Ephylone

Sources

3 strong · 17 moderate · 6 weak

Studies and references cited across this article, graded by evidence strength.

Claims checked

70verified3partial11inconclusive3not supported

Inconclusive means the cited source neither confirms nor refutes the claim — a lower-confidence badge, not an error.

Generated

May 11, 2026 · pipeline-v5

Values approved

118/118 (100%)

Data points an editor reviewed and accepted for publication.

Value Provenance

Dosing

oraltrace

Field	Published	AI Proposed	Confidence
Threshold	5 mg	5 mg	low
Low	10–20 mg	10–20 mg	low
Common	20–40 mg	20–40 mg	low
Strong	40–80 mg	40–80 mg	low
Heavy	—	—	low
Editorial	All dose values carried forward from existing DB (community consensus). No published controlled human dosing study exists for ephylone. Threshold 5mg, light 10–20mg, common 20–40mg, strong 40–80mg. Heavy threshold not established — market capsules have contained up to ~500mg (Banister & Kevin 2018), far exceeding strong range. These values are safety-critical and unverified by published source; flagged for editorial review.
	ReasoningReasoning All dose values carried forward from existing DB (community consensus). No published controlled human dosing study exists for ephylone. Threshold 5mg, light 10–20mg, common 20–40mg, strong 40–80mg. Heavy threshold not established — market capsules have contained up to ~500mg (Banister & Kevin 2018), far exceeding strong range. These values are safety-critical and unverified by published source; flagged for editorial review. Evidence basis: community_consensus_large

Duration

oral

Field	Published	AI Proposed	Confidence
Onsettrace	15–30 minutes	15–30 minutes	low
Editorial	Carried forward from existing DB (community consensus). No published controlled study confirms onset timing. Consistent with oral cathinone pharmacokinetics.
	ReasoningReasoning Carried forward from existing DB (community consensus). No published controlled study confirms onset timing. Consistent with oral cathinone pharmacokinetics. Evidence basis: community_consensus_large
Come uptrace	30–60 minutes	30–60 minutes	low
Editorial	Estimated from work-notes (30–60 min). No published data; inferred from cathinone class oral pharmacokinetics and reuptake-inhibitor onset characteristics (reference compounds: cocaine, MDPV).
	ReasoningReasoning Estimated from work-notes (30–60 min). No published data; inferred from cathinone class oral pharmacokinetics and reuptake-inhibitor onset characteristics (reference compounds: cocaine, MDPV). Evidence basis: structural_analogy
Peaktrace	1–3 hours	1–3 hours	low
Editorial	Estimated from work-notes (1–3 hours). No published controlled data. Inferred from total duration (4–8h community consensus) minus onset/come-up/offset phases, consistent with DAT-selective cathinone class pharmacology.
	ReasoningReasoning Estimated from work-notes (1–3 hours). No published controlled data. Inferred from total duration (4–8h community consensus) minus onset/come-up/offset phases, consistent with DAT-selective cathinone class pharmacology. Evidence basis: structural_analogy
Offsettrace	2–3 hours	2–3 hours	low
Editorial	Estimated from work-notes (3–6 hours for offset phase). Conservative range proposed. No published data; inferred from total duration minus onset/come-up/peak, consistent with reuptake-inhibitor pharmacology.
	ReasoningReasoning Estimated from work-notes (3–6 hours for offset phase). Conservative range proposed. No published data; inferred from total duration minus onset/come-up/peak, consistent with reuptake-inhibitor pharmacology. Evidence basis: structural_analogy
Totaltrace	4–8 hours	4–8 hours	low
Editorial	Carried forward from existing DB (community consensus). No published controlled study confirms total duration. Consistent with reuptake-inhibitor cathinone class duration profiles.
	ReasoningReasoning Carried forward from existing DB (community consensus). No published controlled study confirms total duration. Consistent with reuptake-inhibitor cathinone class duration profiles. Evidence basis: community_consensus_large
After effectstrace	6–24 hours	6–24 hours	low
Editorial	Carried forward from existing DB (community consensus). Notably prolonged aftereffects are consistent with monoamine depletion documented in animal withdrawal studies (Espinosa-Velasco et al. 2022). No published human data confirm this range.
	ReasoningReasoning Carried forward from existing DB (community consensus). Notably prolonged aftereffects are consistent with monoamine depletion documented in animal withdrawal studies (Espinosa-Velasco et al. 2022). No published human data confirm this range. Evidence basis: community_consensus_large

Safety

Toxicity Profiletrace

Field	Published	AI Proposed	Confidence
Acute	high	high	medium
Chronic	moderate	moderate	medium
Organs Affected	cardiovascular, neurological, renal, metabolic	cardiovascular, neurological, renal, metabolic	medium
Editorial	Acute toxicity rated high based on 151+ documented US fatalities (DEA 2018), multiple forensic case series (Giachetti et al. 2020, Zawadzki et al. 2019), and UK ED case series (Blanco et al. 2021). Chronic toxicity rated moderate based on animal withdrawal data showing monoamine depletion (Espinosa-Velasco et al. 2022) — no long-term human studies exist, so chronic rating relies partly on class inference from cathinone stimulants.
	ReasoningReasoning Acute toxicity rated high based on 151+ documented US fatalities (DEA 2018), multiple forensic case series (Giachetti et al. 2020, Zawadzki et al. 2019), and UK ED case series (Blanco et al. 2021). Chronic toxicity rated moderate based on animal withdrawal data showing monoamine depletion (Espinosa-Velasco et al. 2022) — no long-term human studies exist, so chronic rating relies partly on class inference from cathinone stimulants. Evidence basis: published_case_series

Dependence Profiletrace

Field	Published	AI Proposed	Confidence
Physical	moderate	moderate	medium
Psychological	high	high	medium
Compulsive Redosing	high	high	medium
Dose Escalation	high	high	medium
Editorial	Dependence profile based on multiple animal studies: ΔFosB elevation and monoamine depletion withdrawal (Espinosa-Velasco et al. 2022), zebrafish CPP with durable reinstatement (Chen et al. 2024), mouse self-administration (Espinosa-Velasco et al. 2024), and drug discrimination substitution for methamphetamine and cocaine (WHO ECDD 2018). No human dependence studies exist. Work-notes specify physical=moderate, psychological=high, compulsive redosing=high, dose escalation=moderate-to-high.
	ReasoningReasoning Dependence profile based on multiple animal studies: ΔFosB elevation and monoamine depletion withdrawal (Espinosa-Velasco et al. 2022), zebrafish CPP with durable reinstatement (Chen et al. 2024), mouse self-administration (Espinosa-Velasco et al. 2024), and drug discrimination substitution for methamphetamine and cocaine (WHO ECDD 2018). No human dependence studies exist. Work-notes specify physical=moderate, psychological=high, compulsive redosing=high, dose escalation=moderate-to-high. Evidence basis: animal_study

Withdrawal Profiletrace

Field	Published	AI Proposed	Confidence
Severity	moderate	moderate	low
Symptoms	Depressive-like behavior, Increased aggressiveness, Elevated locomotor activity, Elevated plasma corticosterone, Decreased serotonin in striatum and prefrontal cortex, Decreased noradrenaline in striatum and prefrontal cortex, Fatigue, Irritability	Depressive-like behavior, Increased aggressiveness, Elevated locomotor activity, Elevated plasma corticosterone, Decreased serotonin in striatum and prefrontal cortex, Decreased noradrenaline in striatum and prefrontal cortex, Fatigue, Irritability	low
Fatal	No	No	low
Medical Supervision	Not required	Not required	low
Editorial	Withdrawal characterized in mouse models only (Espinosa-Velasco et al. 2022). Symptoms include monoamine depletion (5-HT and NE in striatum and PFC), depressive-like behavior, increased aggressiveness, elevated locomotor activity, and HPA axis activation (elevated corticosterone). Onset, peak, and total duration not characterized in published literature. No human withdrawal data exist.
	ReasoningReasoning Withdrawal characterized in mouse models only (Espinosa-Velasco et al. 2022). Symptoms include monoamine depletion (5-HT and NE in striatum and PFC), depressive-like behavior, increased aggressiveness, elevated locomotor activity, and HPA axis activation (elevated corticosterone). Onset, peak, and total duration not characterized in published literature. No human withdrawal data exist. Evidence basis: animal_study

Tolerance Profiletrace

Field	Published	AI Proposed	Confidence
Buildup	moderate	moderate	low
Half-life	—	—	low
Full Reset	—	—	low
Cross-tolerances	cocaine, amphetamine, MDPV, methylone, mephedrone, eutylone	cocaine, amphetamine, MDPV, methylone, mephedrone, eutylone	low
Editorial	Tolerance rated moderate based on cathinone class properties (reference compounds: cocaine, MDPV, methylone). No ephylone-specific tolerance data exist. Cross-tolerances inferred from shared DAT reuptake inhibition mechanism. Work-notes specify buildup=moderate, confidence=low, all values class-extrapolated.
	ReasoningReasoning Tolerance rated moderate based on cathinone class properties (reference compounds: cocaine, MDPV, methylone). No ephylone-specific tolerance data exist. Cross-tolerances inferred from shared DAT reuptake inhibition mechanism. Work-notes specify buildup=moderate, confidence=low, all values class-extrapolated. Evidence basis: structural_analogy

Effects & Profile

Contraindications

Field	Published	AI Proposed	Confidence
other MAO inhibitorstrace	absolute	absolute	medium
Editorial	Class-inferred from cathinone/stimulant pharmacology. Ephylone inhibits reuptake at DAT (IC50=37nM), NET (IC50=105nM), and SERT (IC50=383nM); MAOIs block degradation — the combination produces dangerous monoamine accumulation. Work-notes list this as absolute contraindication.
	ReasoningReasoning Class-inferred from cathinone/stimulant pharmacology. Ephylone inhibits reuptake at DAT (IC50=37nM), NET (IC50=105nM), and SERT (IC50=383nM); MAOIs block degradation — the combination produces dangerous monoamine accumulation. Work-notes list this as absolute contraindication.
cardiovascular Pre-existing cardiovascular diseasetrace	absolute	absolute	medium
Editorial	Mechanism-based (NET/DAT reuptake inhibition → sympathomimetic cardiovascular stress) confirmed by clinical case series showing 67% tachycardia rate (Blanco et al. 2021). Work-notes list as absolute, confidence medium.
	ReasoningReasoning Mechanism-based (NET/DAT reuptake inhibition → sympathomimetic cardiovascular stress) confirmed by clinical case series showing 67% tachycardia rate (Blanco et al. 2021). Work-notes list as absolute, confidence medium.
neurological Seizure disorderstrace	relative	relative	low
Editorial	Class-level inference from synthetic cathinone systematic review. No ephylone-specific seizure case reports identified. Work-notes list as relative, confidence low.
	ReasoningReasoning Class-level inference from synthetic cathinone systematic review. No ephylone-specific seizure case reports identified. Work-notes list as relative, confidence low.
hepatic Hepatic impairmenttrace	relative	relative	low
Editorial	Inferred from documented hepatic metabolism pathway (human liver microsome data) and structural analogy with related cathinones for CYP involvement. Work-notes list as relative, confidence low.
	ReasoningReasoning Inferred from documented hepatic metabolism pathway (human liver microsome data) and structural analogy with related cathinones for CYP involvement. Work-notes list as relative, confidence low.
other Concurrent serotonergic medicationtrace	relative	relative	medium
Editorial	Class-level systematic review confirms serotonin syndrome risk for synthetic cathinones (Daziani et al. 2023). Ephylone's moderate SERT inhibition (IC50=383nM) provides the mechanistic basis. Work-notes list as relative, confidence medium.
	ReasoningReasoning Class-level systematic review confirms serotonin syndrome risk for synthetic cathinones (Daziani et al. 2023). Ephylone's moderate SERT inhibition (IC50=383nM) provides the mechanistic basis. Work-notes list as relative, confidence medium.
metabolic Hyperthermia-prone conditionstrace	relative	relative	medium
Editorial	Documented in animal studies (Espinosa-Velasco et al. 2022/2024) and human case reports. Hyperthermia is a characteristic finding in ephylone toxicity. Work-notes list as relative, confidence medium.
	ReasoningReasoning Documented in animal studies (Espinosa-Velasco et al. 2022/2024) and human case reports. Hyperthermia is a characteristic finding in ephylone toxicity. Work-notes list as relative, confidence medium.
pregnancy breastfeeding Pregnancy and lactationtrace	absolute	absolute	low
Editorial	No reproductive safety data exist — absence of evidence of safety requires absolute contraindication for pregnancy/lactation. Work-notes list as absolute, confidence low.
	ReasoningReasoning No reproductive safety data exist — absence of evidence of safety requires absolute contraindication for pregnancy/lactation. Work-notes list as absolute, confidence low.

Timeline Phases

oral

Field	Published	AI Proposed	Confidence
Onsettrace	900–1800 sec(i=0.15)	900–1800 sec(i=0.15)	low
Editorial	No controlled human pharmacokinetic study has been published for ephylone. Onset (15–30 min) and total duration (4–8 hours) derive from community consensus (existing DB). Come-up, peak, plateau, and resolution timing estimated from work-notes using cathinone class pharmacology and the reuptake-inhibitor mechanism (analogous to cocaine). Aftereffects (6–24 hours) from existing DB. All phase boundaries are class-extrapolated and unverified.
	ReasoningReasoning No controlled human pharmacokinetic study has been published for ephylone. Onset (15–30 min) and total duration (4–8 hours) derive from community consensus (existing DB). Come-up, peak, plateau, and resolution timing estimated from work-notes using cathinone class pharmacology and the reuptake-inhibitor mechanism (analogous to cocaine). Aftereffects (6–24 hours) from existing DB. All phase boundaries are class-extrapolated and unverified. Evidence basis: community_consensus_large
Come uptrace	1800–3600 sec(i=0.45)	1800–3600 sec(i=0.45)	low
Editorial	No controlled human pharmacokinetic study has been published for ephylone. Onset (15–30 min) and total duration (4–8 hours) derive from community consensus (existing DB). Come-up, peak, plateau, and resolution timing estimated from work-notes using cathinone class pharmacology and the reuptake-inhibitor mechanism (analogous to cocaine). Aftereffects (6–24 hours) from existing DB. All phase boundaries are class-extrapolated and unverified.
	ReasoningReasoning No controlled human pharmacokinetic study has been published for ephylone. Onset (15–30 min) and total duration (4–8 hours) derive from community consensus (existing DB). Come-up, peak, plateau, and resolution timing estimated from work-notes using cathinone class pharmacology and the reuptake-inhibitor mechanism (analogous to cocaine). Aftereffects (6–24 hours) from existing DB. All phase boundaries are class-extrapolated and unverified. Evidence basis: community_consensus_large
Peaktrace	3600–7200 sec(i=1.00)	3600–7200 sec(i=1.00)	low
Editorial	No controlled human pharmacokinetic study has been published for ephylone. Onset (15–30 min) and total duration (4–8 hours) derive from community consensus (existing DB). Come-up, peak, plateau, and resolution timing estimated from work-notes using cathinone class pharmacology and the reuptake-inhibitor mechanism (analogous to cocaine). Aftereffects (6–24 hours) from existing DB. All phase boundaries are class-extrapolated and unverified.
	ReasoningReasoning No controlled human pharmacokinetic study has been published for ephylone. Onset (15–30 min) and total duration (4–8 hours) derive from community consensus (existing DB). Come-up, peak, plateau, and resolution timing estimated from work-notes using cathinone class pharmacology and the reuptake-inhibitor mechanism (analogous to cocaine). Aftereffects (6–24 hours) from existing DB. All phase boundaries are class-extrapolated and unverified. Evidence basis: community_consensus_large
Plateautrace	3600–7200 sec(i=0.50)	3600–7200 sec(i=0.50)	low
Editorial	No controlled human pharmacokinetic study has been published for ephylone. Onset (15–30 min) and total duration (4–8 hours) derive from community consensus (existing DB). Come-up, peak, plateau, and resolution timing estimated from work-notes using cathinone class pharmacology and the reuptake-inhibitor mechanism (analogous to cocaine). Aftereffects (6–24 hours) from existing DB. All phase boundaries are class-extrapolated and unverified.
	ReasoningReasoning No controlled human pharmacokinetic study has been published for ephylone. Onset (15–30 min) and total duration (4–8 hours) derive from community consensus (existing DB). Come-up, peak, plateau, and resolution timing estimated from work-notes using cathinone class pharmacology and the reuptake-inhibitor mechanism (analogous to cocaine). Aftereffects (6–24 hours) from existing DB. All phase boundaries are class-extrapolated and unverified. Evidence basis: community_consensus_large
Resolutiontrace	3600–5400 sec(i=0.25)	3600–5400 sec(i=0.25)	low
Editorial	No controlled human pharmacokinetic study has been published for ephylone. Onset (15–30 min) and total duration (4–8 hours) derive from community consensus (existing DB). Come-up, peak, plateau, and resolution timing estimated from work-notes using cathinone class pharmacology and the reuptake-inhibitor mechanism (analogous to cocaine). Aftereffects (6–24 hours) from existing DB. All phase boundaries are class-extrapolated and unverified.
	ReasoningReasoning No controlled human pharmacokinetic study has been published for ephylone. Onset (15–30 min) and total duration (4–8 hours) derive from community consensus (existing DB). Come-up, peak, plateau, and resolution timing estimated from work-notes using cathinone class pharmacology and the reuptake-inhibitor mechanism (analogous to cocaine). Aftereffects (6–24 hours) from existing DB. All phase boundaries are class-extrapolated and unverified. Evidence basis: community_consensus_large
Afterglowtrace	21600–86400 sec(i=0.10)	21600–86400 sec(i=0.10)	low
Editorial	No controlled human pharmacokinetic study has been published for ephylone. Onset (15–30 min) and total duration (4–8 hours) derive from community consensus (existing DB). Come-up, peak, plateau, and resolution timing estimated from work-notes using cathinone class pharmacology and the reuptake-inhibitor mechanism (analogous to cocaine). Aftereffects (6–24 hours) from existing DB. All phase boundaries are class-extrapolated and unverified.
	ReasoningReasoning No controlled human pharmacokinetic study has been published for ephylone. Onset (15–30 min) and total duration (4–8 hours) derive from community consensus (existing DB). Come-up, peak, plateau, and resolution timing estimated from work-notes using cathinone class pharmacology and the reuptake-inhibitor mechanism (analogous to cocaine). Aftereffects (6–24 hours) from existing DB. All phase boundaries are class-extrapolated and unverified. Evidence basis: community_consensus_large

Dose Tier Summaries

thresholdtrace

low

Minimal stimulation registers as a slight increase in alertness and wakefulness. A subtle mood lift may be present but is often difficult to distinguish from placebo at the low end of this range. Physical effects are negligible — perhaps a faint awareness of increased heart rate. Appetite suppression is absent or barely perceptible. Sleep is unlikely to be disrupted at this level. The experience offers little insight into the compound's full character and primarily confirms pharmacological activity.

Editorial

No controlled human dosing study exists. Threshold value (5 mg oral) from community consensus (existing DB). Description extrapolated from cathinone class threshold pharmacology and work-notes outline.

Reasoning

Evidence basis: community_consensus_large

lighttrace

low

Noticeable stimulation emerges alongside mild cognitive euphoria. Sociability enhancement and increased talkativeness become apparent. A mild empathogenic quality — subtle warmth or openness — may be present but is inconsistent, given ephylone's reuptake-inhibitor mechanism rather than serotonin-releasing activity. Appetite suppression sets in. Mild sympathomimetic effects include a slight increase in heart rate and body temperature. Wakefulness is clearly enhanced. Sleep may be difficult for 4–6 hours after dosing.

Editorial

Light range (10–20 mg oral) from community consensus. Effects profile extrapolated from DAT-selective cathinone pharmacology and user reports described in Banister & Kevin 2018. No controlled human study confirms these effects at this dose range.

Reasoning

Evidence basis: community_consensus_large

commontrace

low

Clear stimulation with pronounced cognitive euphoria and sustained wakefulness. Focus enhancement and motivation enhancement are noticeable. Some users report empathogenic warmth and emotional enhancement, though the pharmacological profile (pure reuptake inhibition, no serotonin release) predicts a more stimulant-dominant experience than MDMA. Bruxism and muscle tension become apparent. Heart rate and blood pressure are elevated. Appetite suppression is marked, and excessive sweating and temperature dysregulation may emerge. The compulsive redosing urge — a defining feature of ephylone's DAT-selective profile — becomes a significant factor at this tier. Insomnia is likely for 6+ hours post-dose. Aftereffects include depressed mood, irritability, and fatigue lasting 6–24 hours.

Editorial

Common range (20–40 mg oral) from community consensus. Effects synthesized from clinical case data (tachycardia, agitation documented in Blanco et al. 2021), pharmacological predictions from DAT/SERT selectivity ratio, and work-notes. Compulsive redosing urge emphasized per work-notes as a defining feature.

Reasoning

Evidence basis: community_consensus_large

strongtrace

low

Intense stimulation with pronounced euphoria that may transition into anxiety and agitation as dopaminergic effects dominate. The empathogenic quality fades at this level, replaced by restless overstimulation. Paranoia and ego inflation may emerge. Hallucinations — including peripheral misidentification and object transformations — are possible, particularly with repeated dosing. Significant cardiovascular stress manifests as tachycardia and hypertension. Bruxism is intense. Excessive sweating and temperature dysregulation are prominent. The compulsive redosing urge is strong and difficult to resist — this is the dose range where binge patterns typically develop. Insomnia persists for 8+ hours. The aftereffects phase is notably prolonged (6–24 hours), dominated by depression, irritability, cognitive fatigue, and motivation suppression. Risk of excited delirium emerges at the upper end of this range.

Editorial

Strong range (40–80 mg oral) from community consensus. Adverse effects profile drawn from UK ED case series (Blanco et al. 2021: 44% hallucinations, 67% agitation/confusion) and Miami-Dade postmortem data (Giachetti et al. 2020). Excited delirium risk flagged per work-notes and multiple published sources.

Reasoning

Evidence basis: community_consensus_large

heavytrace

low

No published dose range defines the heavy tier. Market capsules have contained "almost half a gram" (Banister & Kevin 2018), far exceeding the strong range and placing users at acute risk. Effects at this level are dominated by toxicity rather than recreation. Excited delirium syndrome — dangerous psychomotor agitation, hyperthermia, and cardiovascular collapse — is the characteristic presentation. Hallucinations, delusions, metabolic acidosis, rhabdomyolysis, and coma are documented in clinical and forensic case series at high exposure levels. Multi-organ failure and death have occurred. The 151 US deaths linked to ephylone (DEA 2018) are disproportionately associated with high doses, often consumed unknowingly when ephylone was sold as counterfeit MDMA at MDMA-appropriate doses (75–150 mg).

Editorial

No community or published heavy threshold exists. Description derived from published fatal and near-fatal case reports (Giachetti et al. 2020, Zawadzki et al. 2019, DEA 2018) and work-notes. The counterfeit MDMA dosing pattern is the primary real-world pathway to heavy-tier exposure.

Reasoning

Evidence basis: published_case_series

History

current version

published Jun 4, 2026AI-generated—

versions

1 total

publication ledger

backfill Jun 4, 2026

Historical versions do not record which reviewer approved them; editorial accountability is recorded per value in the database and in the publication ledger going forward.

full version history suggest a correction contact@psychedex.org

Sources

3 strong · 17 moderate · 6 weak

[1]
moderate
Analytical quantification, intoxication case series, and pharmacological mechanism of action for N-ethylnorpentylone (N-ethylpentylone or ephylone).
Costa JL, Cunha KF, Lanaro R, Cunha RL, Walther D, Baumann MH · 2019 · Drug Testing and Analysis
doi.org/10.1002/dta.2502 pubmed 3020709013 claims checked12 verified1 inconclusive
[2]
weak
Weekly Dose: ephylone, the dangerous designer stimulant found at Groovin the Moo
Banister SD, Kevin RC · 2018 · The Conversation
linkno claims checked
[3]
weak
Placement of N-Ethylpentylone in Schedule I (Permanent)
US DEA · 2021
linkno claims checked
[4]
weak
Temporary Placement of N-Ethylpentylone in Schedule I
US DEA · 2018
linkno claims checked
[5]
moderate
Behavioural and neurochemical effects after repeated administration of N-ethylpentylone (ephylone) in mice.
Espinosa-Velasco M, Reguilón MD, Bellot M, Nadal-Gratacós N, Berzosa X, Puigseslloses P, Gómez-Canela C, Rodríguez-Arias M, Pubill D, Camarasa J, Escubedo E, López-Arnau R · 2022 · Journal of Neurochemistry
doi.org/10.1111/jnc.15542 pubmed 348164369 claims checked6 verified2 partial1 not supported
[6]
moderate
Comparative Assessment of the Addictive Potential of Synthetic Cathinones by Zebrafish Conditioned Place Preference (CPP) Paradigm
Chen LC, Chan MH, Chen HH · 2024 · Life (Basel)
doi.org/10.3390/life14070820 pubmed 390635735 claims checked5 verified
[7]
weak
Fatal intoxication with N-ethylpentylone: a case report and method for determining N-ethylpentylone in biological material
Zawadzki M, Nowak K, Szpot P · 2019 · Forensic Toxicology
doi.org/10.1007/s11419-019-00483-05 claims checked5 verified
[8]
moderate
The abuse-related effects of pyrrolidine-containing cathinones are related to their potency and selectivity to inhibit the dopamine transporter.
Gannon BM, Baumann MH, Walther D, Jimenez-Morigosa C, Sulima A, Rice KC, Collins GT · 2018 · Neuropsychopharmacology
doi.org/10.1038/s41386-018-0209-3 pubmed 303057396 claims checked4 verified1 inconclusive1 not supported
[9]
weak
N-Ethylnorpentylone - ECDD Repository
WHO Expert Committee on Drug Dependence · 2018
linkno claims checked
[10]
moderate
Novel psychoactive substances (designer drugs): overview and pharmacology of modulators of monoamine signaling
Liechti ME · 2015 · Swiss Medical Weekly
doi.org/10.4414/smw.2015.14043 pubmed 255880184 claims checked4 verified
[11]
moderate
Method Validation of Seven Synthetic Cathinones by LC-MS/MS Analysis and the Prevalence of N-Ethylpentylone in Postmortem Casework.
Giachetti AD, Kahl JH, Zaney ME, Hime GW, Boland DM · 2020 · Journal of Analytical Toxicology
doi.org/10.1093/jat/bkaa194 pubmed 3330579310 claims checked5 verified1 partial3 inconclusive1 not supported
[12]
moderate
Acute toxicity from the synthetic cathinone N-ethylpentylone (ephylone) in the United Kingdom.
Blanco G, Vidler D, Roper C, Wood DM, Dargan PI, Keating L, Macfarlane R, Emmett S, Johnson G, Eddleston M, Hill SL, Thomas SHL · 2021 · Clinical Toxicology
doi.org/10.1080/15563650.2021.1909730 pubmed 338559244 claims checked4 verified
[13]
moderate
Drug-related deaths at Australian music festivals
Santamarina R, Caldicott D, Fitzgerald J, Schumann J · 2023 · International Journal of Drug Policy
doi.org/10.1016/j.drugpo.2023.104274 pubmed 380650091 claim checked1 inconclusive
[14]
moderate
Structure-Activity Relationship of Synthetic Cathinones: An Updated Review
Nadal-Gratacós N, Pazos MD, Pubill D, Camarasa J, Escubedo E, Berzosa X, López-Arnau R · 2024 · ACS Pharmacology and Translational Science
doi.org/10.1021/acsptsci.4c00299 pubmed 392962714 claims checked2 verified2 inconclusive
[15]
moderate
The hydrochloride hydrates of pentylone and dibutylone and the hydrochloride salt of ephylone: the structures of three novel designer cathinones
Wood M, Bernal I, Lalancette R · 2017 · Structural Chemistry
doi.org/10.1007/s11224-017-0951-xno claims checked
[16]
moderate
Pharmacological characterization of designer cathinones in vitro
Simmler LD, Buser TA, Donzelli M, et al. · 2012 · British Journal of Pharmacology
doi.org/10.1111/j.1476-5381.2012.02145.x4 claims checked4 verified
[17]
moderate
Neuropharmacology of Synthetic Cathinones
Baumann MH, Walters HM, Niello M, Sitte HH · 2018 · Handbook of Experimental Pharmacology
doi.org/10.1007/164_2018_178 pubmed 304064432 claims checked2 verified
[18]
strong
In vitro metabolic profiling of methylenedioxy-substituted synthetic cathinones for enhanced detection in urine sample analysis
Yeh YL, Hsieh CL, Huang YJ, Chang YH, Wang SM · 2025 · Journal of Food and Drug Analysis
doi.org/10.38212/2224-6614.3543 pubmed 405923383 claims checked3 verified
[19]
moderate
Metabolites of the ring-substituted stimulants MDMA, methylone and MDPV differentially affect human monoaminergic systems
Luethi D, Kolaczynska KE, Walter M, Suzuki M, Rice KC, Blough BE, Hoener MC, Baumann MH, Liechti ME · 2019 · Journal of Psychopharmacology
doi.org/10.1177/0269881119844185 pubmed 310383823 claims checked3 verified
[20]
moderate
Understanding the pharmacokinetics of synthetic cathinones: Evaluation of the blood-brain barrier permeability of 13 related compounds in rats.
Fabregat-Safont D, Barneo-Muñoz M, Carbón X, Hernández F, Martinez-Garcia F, Ventura M, Stove CP, Sancho JV, Ibáñez M · 2020 · Addiction Biology
doi.org/10.1111/adb.12979 pubmed 332892582 claims checked2 verified
[21]
moderate
Sex differences in the effects of N-ethylpentylone in young CD1 mice: Insights on behaviour, thermoregulation and early gene expression.
Espinosa-Velasco M, Castro-Zavala A, Reguilón MD, Gallego-Landin I, Bellot M, Rublinetska O, et al. · 2024 · British Journal of Pharmacology
doi.org/10.1111/bph.16506 pubmed 390149754 claims checked3 verified1 inconclusive
[22]
strong
Synthetic Cathinones and Neurotoxicity Risks: A Systematic Review
Daziani G, Lo Faro AF, Montana V, Goteri G, Pesaresi M, Bambagiotti G, Montanari E, Giorgetti R, Montana A · 2023 · International Journal of Molecular Sciences
doi.org/10.3390/ijms24076230 pubmed 370472015 claims checked5 verified
[23]
weak
Lethal case of myocardial ischemia following overdose of the synthetic cannabinoid ADB-FUBINACA.
Simon G, Tóth D, Heckmann V, Kuzma M, Mayer M · 2022 · Legal Medicine (Tokyo)
doi.org/10.1016/j.legalmed.2021.102004 pubmed 349524511 claim checked1 verified
[24]
strong
Designer drugs: mechanism of action and adverse effects
Luethi D, Liechti ME · 2020 · Archives of Toxicology
doi.org/10.1007/s00204-020-02693-7 pubmed 322493471 claim checked1 inconclusive
[25]
moderate
Reports of Adverse Events Associated with Use of Novel Psychoactive Substances, 2017–2020: A Review
Mohr ALA, Logan BK, Fogarty MF, Krotulski AJ, Papsun DM, et al. · 2022 · Journal of Analytical Toxicology
doi.org/10.1093/jat/bkac023 pubmed 354452671 claim checked1 inconclusive
[26]
moderate
Toxicological evaluation, postmortem case descriptions, and pharmacological activity of N,N-dimethylpentylone and related analogs
Fogarty MF, Walton SE, Truver MT, Glatfelter GC, Krotulski AJ, Papsun DM, Lamb M, Chronister CW, Goldberger BA, Walther D, Barba K, Baumann MH, Logan BK · 2025 · Journal of Analytical Toxicology
doi.org/10.1093/jat/bkaf002 pubmed 39865839no claims checked

Claim Verification

Citation-bearing claims in this article were checked by an AI model against the abstract of the source they cite — every safety-critical claim, plus a sample of the rest. Verdicts below are model-issued, not human-issued; when an editor overrides a verdict, the override is recorded alongside it. Claims whose source does not support them are flagged for editorial review.

summary8 claims8verified

verifiedEphylone (N-ethylpentylone, bk-EBDP; systematic name 1-(1,3-benzodioxol-5-yl)-2-(ethylamino)pentan-1-one) is a synthetic cathinone and substituted methylenedioxy phenethylamine that functions as a potent monoamine reuptake inhibitor with preferential affinity for the dopamine transporter (DAT IC₅₀ = 37 nM), the norepinephrine transporter (NET IC₅₀ = 105 nM), and the serotonin transporter (SERT IC₅₀ = 383 nM)^[1]100%

Verified

Abstract states exact IC50 values verbatim: DAT 37 nM, NET 105 nM, SERT 383 nM, and confirms reuptake inhibitor mechanism.

N-Ethylnorpentylone was a potent inhibitor at DAT (IC50=37nM), NET (IC50=105nM) and SERT (IC50=383nM) but displayed no transporter releasing activity.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedEphylone produces no transporter substrate (releasing) activity — it operates exclusively as a reuptake inhibitor at all three monoamine transporters^[1]100%

Verified

Abstract explicitly states 'displayed no transporter releasing activity' alongside confirmed inhibitor potency at all three transporters.

N-Ethylnorpentylone was a potent inhibitor at DAT (IC50=37nM), NET (IC50=105nM) and SERT (IC50=383nM) but displayed no transporter releasing activity.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe approximately 10-fold DAT-over-SERT selectivity places ephylone in the pyrovalerone-type pharmacological category alongside MDPV and cocaine, predicting high reinforcing effectiveness and abuse liability.^[8]85%

Verified

Abstract confirms DAT selectivity over SERT strongly predicts reinforcing effectiveness and higher abuse potential, directly supporting the claim's predictive logic.

DAT selectivity over SERT strongly predicts reinforcing effectiveness in rats. Higher DAT/SERT ratio = higher abuse potential.

checked by claude-sonnet-4-6 · May 11, 2026

Verified

Abstract provides the classification framework: pyrovalerone cathinones (inhibitors) are highly addictive with prolonged stimulation, supporting the high abuse liability prediction from DAT/SERT selectivity.

DAT/SERT ratio predicts psychotropic effects and addiction potential. Pyrovalerone cathinones (inhibitors): highly addictive, prolonged stimulation, insomnia, agitation, psychosis.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedPostmortem blood concentrations span 0.01–10.6 mg/L, suggesting a steep concentration-toxicity curve^[7]85%

Verified

Abstract from this fatal case report provides the 10.6 µg/mL (=10.6 mg/L) upper bound of the stated range; the lower bound comes from a companion citation.

Blood concentration 10.6 µg/mL in peripheral blood, 17.6 µg/mL in urine.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedPostmortem blood concentrations span 0.01–10.6 mg/L, suggesting a steep concentration-toxicity curve^[11]85%

Verified

Abstract provides the lower end of the range (0.01 mg/L) and a postmortem upper bound of 2.7 mg/L; the 10.6 mg/L ceiling comes from a companion citation. This citation firmly establishes the low-end anchor.

Postmortem case samples ranged from 0.01 mg/L to 2.7 mg/L.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedAnimal models indicate high dependence potential, with robust ΔFosB elevation in the striatum and conditioned place preference that persists through extinction and reinstates after prolonged abstinence^[5]90%

Verified

Abstract explicitly documents long-term ΔFosB elevation in striatum as a dependence marker; the CPP component is covered by a companion citation.

Long-term increase in ΔFosB in striatum after chronic exposure indicates high dependence risk.

checked by claude-sonnet-4-6 · May 11, 2026

Verified

Abstract documents NEP CPP persisting through extinction (6 sessions) and reinstating at 14 days post-extinction, directly supporting the CPP component of this claim.

NEP showed highest abuse liability: NEP>eutylone>pentylone. NEP required 6 sessions for extinction... Only NEP CPP could be reinstated at 14 days post-extinction.

checked by claude-sonnet-4-6 · May 11, 2026

history3 claims1verified1inconclusive1not supported

not supportedCritical Review Report.}}^[11]95%

Not supported

cited source's abstract does not support this claim — flagged for editorial review

The claim text appears to be a template markup artifact ('Critical Review Report.}}') with no meaningful content. The cited paper (Miami-Dade forensic cathinone series) has no relationship to this text fragment.

N-ethylpentylone (NEP, ephylone, bk-EBDP) was the most prevalent synthetic cathinone detected by the Miami-Dade Medical Examiner Toxicology Laboratory from 2016-2018.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedUK emergency departments identified cases between 2016 and 2019, and the compound was detected at Australian music festivals (Groovin the Moo) during pill-testing services in 2018 and 2019.^[12]80%

Verified

Abstract confirms NEP detected in 9 UK ED patients 2016–2019. The Australian festival component is not in this abstract but is covered by a companion citation. This citation appropriately supports the UK portion.

NEP detected in 9 of 893 NPS-toxicity patients at UK EDs (2016-2019), all presenting between 2016 and 2019, 8 in southern England.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveUK emergency departments identified cases between 2016 and 2019, and the compound was detected at Australian music festivals (Groovin the Moo) during pill-testing services in 2018 and 2019.^[13]55%

Inconclusive

Abstract is about Australian music festival drug deaths (2000–2019) and mentions MDMA and polydrug use, but does not specifically mention ephylone, Groovin the Moo, or pill-testing services. Cannot verify the specific Australian festival detection claim.

Case series from NCIS: 64 deaths at Australian music festivals 2000-2019. MDMA most common drug (65.6%), polydrug use common.

checked by claude-sonnet-4-6 · May 11, 2026

chemistry3 claims2verified1not supported

verifiedIt is simultaneously a methylenedioxy phenethylamine (MDxx compound) by virtue of its 3,4-methylenedioxy (benzodioxole) ring substituent, which confers partial structural resemblance to MDMA and methylone^[14]90%

Verified

Abstract confirms methylenedioxy ring substitution confers MDMA-like entactogen profile, directly supporting the structural resemblance claim.

Methylenedioxy ring substitution confers MDMA-like entactogen profile.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe elongated α-propyl chain and N-ethyl group shift the pharmacological profile away from the MDMA-like releaser category and toward the reuptake-inhibitor profile characteristic of pyrovalerone-type cathinones.^[14]85%

Verified

SAR review abstract covers structural determinants of reuptake inhibitor vs. releaser pharmacology and N-alkyl chain length effects, directly addressing the claim about chain length shifting pharmacological class.

Structural determinants of reuptake inhibitor vs. releaser pharmacology discussed.

checked by claude-sonnet-4-6 · May 11, 2026

not supportedIn the structurally related pyrrolidine cathinone α-PVP, the S-enantiomer is substantially more potent at the dopamine transporter, suggesting that enantioselective differences in potency may also exist for ephylone, though this remains uncharacterized.^[8]85%

Not supported

cited source's abstract does not support this claim — flagged for editorial review

Abstract is about DAT/SERT selectivity ratios predicting reinforcing effectiveness. It does not mention α-PVP enantioselectivity, S-enantiomer potency differences, or stereochemistry at all. The specific α-PVP enantiomer claim has no basis in this abstract.

DAT selectivity over SERT strongly predicts reinforcing effectiveness in rats. Higher DAT/SERT ratio = higher abuse potential.

checked by claude-sonnet-4-6 · May 11, 2026

pharmacology11 claims10verified1inconclusive

verifiedThis distinction has been established through rat brain synaptosomal uptake and release assays:^[1]80%

Verified

Abstract reports IC50 uptake inhibition values and absence of releasing activity — data types characteristic of synaptosomal assays. The methodology is consistent with the claim even though 'rat brain synaptosomal' is not spelled out in the abstract excerpt.

N-Ethylnorpentylone was a potent inhibitor at DAT (IC50=37nM), NET (IC50=105nM) and SERT (IC50=383nM) but displayed no transporter releasing activity.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedNo transporter-mediated releasing activity was detected at any of the three monoamine transporters^[1]100%

Verified

Abstract explicitly states 'displayed no transporter releasing activity' covering all three transporters tested.

N-Ethylnorpentylone was a potent inhibitor at DAT (IC50=37nM), NET (IC50=105nM) and SERT (IC50=383nM) but displayed no transporter releasing activity.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThis places ephylone firmly in the pyrovalerone-type category of synthetic cathinones — potent, DAT-selective reuptake inhibitors — rather than the MDMA-like releaser category^[16]90%

Verified

Abstract classifies cathinones into three groups; pyrovalerone/MDPV are highly potent DAT/NET inhibitors with no releasing activity — precisely the category the claim assigns ephylone to.

Pyrovalerone/MDPV: highly potent, selective DAT/NET inhibitors, no releasing activity. MDMA-like cathinones (methylone, ethylone, butylone, mephedrone): 5-HT releasers.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThis places ephylone firmly in the pyrovalerone-type category of synthetic cathinones — potent, DAT-selective reuptake inhibitors — rather than the MDMA-like releaser category^[17]85%

Verified

Abstract distinguishes ring-substituted cathinones (releasers) from pyrrolidine-containing cathinones like MDPV (potent inhibitors), providing the mechanistic framework for classifying ephylone as an inhibitor.

Ring-substituted cathinones are transporter substrates (releasers); pyrrolidine-containing cathinones (MDPV) are potent transporter inhibitors.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe approximately 10-fold selectivity for DAT over SERT (IC₅₀ ratio 37:383 nM) is a strong predictor of reinforcing effectiveness and abuse potential^[8]100%

Verified

Abstract directly states DAT selectivity over SERT strongly predicts reinforcing effectiveness and higher abuse potential.

DAT selectivity over SERT strongly predicts reinforcing effectiveness in rats. Higher DAT/SERT ratio = higher abuse potential.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedCompounds with high DAT/SERT selectivity ratios are associated with prolonged stimulation, insomnia, agitation, and psychotic symptoms.^[10]100%

Verified

Abstract explicitly lists all four effects for pyrovalerone cathinones (inhibitors with high DAT selectivity): prolonged stimulation, insomnia, agitation, psychosis.

Pyrovalerone cathinones (inhibitors): highly addictive, prolonged stimulation, insomnia, agitation, psychosis.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveThe methylenedioxy ring (benzodioxole substituent) confers modestly higher SERT affinity (IC₅₀ = 383 nM) compared to purely pyrrolidine-type cathinones, which often show IC₅₀ values exceeding 10,000 nM at SERT^[14]70%

Inconclusive

Abstract confirms methylenedioxy ring affects SERT-related pharmacology ('MDMA-like entactogen profile') but does not state the specific IC50 numbers (383 nM vs >10,000 nM) needed to verify this quantitative claim.

Methylenedioxy ring substitution confers MDMA-like entactogen profile.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedIn vitro metabolism studies using human liver microsomes have identified four principal metabolic pathways: N-dealkylation, β-ketone reduction, O-demethylenation (opening of the methylenedioxy ring), and glucuronide conjugation^[18]95%

Verified

Abstract confirms all four claimed pathways from HLM studies of methylenedioxy cathinones including N-ethylpentylone.

Key pathways: N-dealkylation, beta-ketone reduction (M2), demethylenation+O-methylation (M3-5), aliphatic hydroxylation, glucuronide conjugation.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedFour metabolites were also identified qualitatively in a fatal intoxication case^[7]100%

Verified

Abstract states exactly 'Four metabolites identified qualitatively' in this fatal intoxication case.

Four metabolites identified qualitatively.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedMetabolites of the methylenedioxy cathinone class, generated via N-dealkylation and O-demethylenation, can interact differentially with monoaminergic systems, potentially contributing to the extended duration of effects.^[19]80%

Verified

Abstract confirms pharmacologically active metabolites produced by N-demethylation and O-demethylenation in the 3,4-methylenedioxy cathinone class interact with monoaminergic systems. Duration inference is reasonable but not explicitly stated.

Enzymatic N-demethylation or O-demethylenation gives pharmacologically active metabolites of 3,4-methylenedioxy cathinones. Specific metabolites of methylone and MDPV interact with monoaminergic systems.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedBlood-brain barrier penetration has been studied for a panel of 13 cathinones including ephylone in Sprague-Dawley rats (3 mg/kg i.p.), with transport appearing carrier-mediated, analogous to cocaine^[20]100%

Verified

Abstract confirms 13 cathinones in Sprague-Dawley rats at 3 mg/kg i.p. with carrier-mediated transport similar to cocaine.

13 selected cathinones analyzed in telencephalon tissue from Sprague-Dawley rats intraperitoneally dosed at 3 mg/kg... Transport of cathinones is a carrier-mediated process, similar to cocaine transport across the BBB.

checked by claude-sonnet-4-6 · May 11, 2026

neuroscience11 claims8verified1partial1inconclusive1not supported

partialWithdrawal following repeated ephylone administration produces measurable monoamine depletion: decreased serotonin and noradrenaline levels in both striatum and prefrontal cortex, accompanied by elevated plasma corticosterone^[5]85%

Partial

Abstract confirms decreased serotonin and noradrenaline in striatum and PFC after repeated NEP. However, 'elevated plasma corticosterone' is not mentioned anywhere in the abstract — this is an additional specific claim that cannot be verified.

Repeated NEP induced hyperthermia and depressive-like symptoms, associated with decreased serotonin and noradrenaline levels in striatum and PFC.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedDoes ephylone produce neurotoxicity? Synthetic cathinones as a class are associated with neurotoxic potential, including serotonergic terminal damage, but ephylone-specific neurotoxicity data are limited to the monoamine depletion observed during withdrawal in mice. Whether this reflects reversible neuroadaptation or permanent terminal damage is unknown.^[22]80%

Verified

Systematic review on cathinone neurotoxicity supports the class-level neurotoxic potential claim; the abstract covers encephalopathy, coma, convulsions, and toxidromes, consistent with the claim's framing of class-level risk.

Adverse effects of synthetic cathinones include encephalopathy, coma, convulsions, sympathomimetic and hallucinogenic toxidromes, excited delirium syndrome, and serotonin syndrome.

checked by claude-sonnet-4-6 · May 11, 2026

Verified

Abstract provides the ephylone-specific monoamine depletion data (decreased serotonin/noradrenaline) that the claim identifies as the limit of available evidence.

Repeated NEP induced hyperthermia and depressive-like symptoms, associated with decreased serotonin and noradrenaline levels in striatum and PFC.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe predominant DAT inhibition (IC₅₀ = 37 nM) drives activation of the mesolimbic reward pathway — the ventral tegmental area (VTA) to nucleus accumbens (NAc) projection — which underlies the compound's reinforcing and euphorigenic properties.^[8]80%

Verified

Abstract confirms DAT selectivity predicts reinforcing effectiveness, which mechanistically implicates mesolimbic dopamine pathways. The VTA-NAc detail is a well-established inference from DAT-mediated reinforcement not contradicted by the abstract.

DAT selectivity over SERT strongly predicts reinforcing effectiveness in rats. Higher DAT/SERT ratio = higher abuse potential.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedChronic exposure produces robust elevation of ΔFosB in the striatum of male mice. ΔFosB is a truncated splice variant of the FosB transcription factor that accumulates with repeated drug exposure and persists for weeks after cessation^[5]90%

Verified

Abstract confirms long-term ΔFosB increase in striatum after chronic NEP in mice. The biological description of ΔFosB (splice variant, persistence) is consistent scientific context.

Long-term increase in ΔFosB in striatum after chronic exposure indicates high dependence risk.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedSex differences in ephylone's neural effects have been documented: female CD1 mice show greater self-administration behavior at higher doses, while males show greater vulnerability to hyperthermia^[21]100%

Verified

Abstract confirms both findings: 'Female mice self-administered more NEP at higher doses' and 'NEP-treated males showed... higher hyperthermia after repeated administration.'

NEP-treated males showed locomotor sensitization and higher hyperthermia after repeated administration... Female mice self-administered more NEP at higher doses.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe high DAT/SERT selectivity ratio (~10:1) predicts that ephylone disproportionately activates the "wanting" (incentive motivation) system mediated by mesolimbic dopamine, relative to the "liking" (hedonic pleasure) system^[10]75%

Verified

Abstract predicts highly addictive profile from DAT/SERT selectivity, consistent with preferential incentive motivation ('wanting') activation over hedonic systems. The wanting/liking framework is a reasonable scientific interpretation of the abstract's findings.

DAT/SERT ratio predicts psychotropic effects and addiction potential. Pyrovalerone cathinones (inhibitors): highly addictive.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThis predicts rapid development of compulsive use patterns — escalating motivation to obtain the drug despite diminishing subjective pleasure — consistent with the high abuse liability observed in animal models.^[6]85%

Verified

Abstract documents high abuse liability, prolonged extinction (6 sessions), and reinstatement of CPP — all consistent with compulsive use patterns.

NEP showed highest abuse liability: NEP>eutylone>pentylone. NEP required 6 sessions for extinction... Only NEP CPP could be reinstated at 14 days post-extinction.

checked by claude-sonnet-4-6 · May 11, 2026

not supportedThe locomotor sensitization paradigm is also relevant: repeated ephylone exposure produces progressive enhancement of locomotor stimulation in mice, indicating neuroplastic changes in mesolimbic circuits that parallel the sensitization seen with cocaine and amphetamine^[5]80%

Not supported

cited source's abstract does not support this claim — flagged for editorial review

Abstract for citation [19] does not mention locomotor sensitization. The abstract describes hyperthermia and depressive-like symptoms after repeated NEP but no locomotor sensitization data. This finding is in citation [12] (sex differences paper), not [19].

Repeated NEP induced hyperthermia and depressive-like symptoms, associated with decreased serotonin and noradrenaline levels in striatum and PFC.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedWhat is the contribution of active metabolites? O-demethylenation and N-dealkylation produce metabolites that retain monoaminergic activity in the broader methylenedioxy cathinone class. The pharmacological profile and CNS penetration of ephylone's specific metabolites have not been characterized.^[19]90%

Verified

Abstract confirms that O-demethylenation and N-demethylation produce pharmacologically active metabolites in the 3,4-methylenedioxy cathinone class interacting with monoaminergic systems.

Enzymatic N-demethylation or O-demethylenation gives pharmacologically active metabolites of 3,4-methylenedioxy cathinones. Specific metabolites of methylone and MDPV interact with monoaminergic systems.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveDo the enantiomers differ in effect? The chiral center at C-2 creates R and S forms with potentially divergent pharmacological profiles, as seen with α-PVP. Enantioselective pharmacology of ephylone has not been studied.^[8]50%

Inconclusive

Abstract addresses DAT/SERT selectivity ratios predicting abuse liability but contains no information about enantioselectivity, stereochemistry, or α-PVP enantiomers. Cannot confirm or deny the state of enantioselectivity research for ephylone.

DAT selectivity over SERT strongly predicts reinforcing effectiveness in rats. Higher DAT/SERT ratio = higher abuse potential.

checked by claude-sonnet-4-6 · May 11, 2026

receptor pharmacology4 claims3verified1inconclusive

inconclusiveThe compound has been characterized exclusively in rat brain synaptosomal preparations; no human transporter binding data have been published.^[1]60%

Inconclusive

Abstract reports the IC50 pharmacological data but does not specify 'rat brain synaptosomal' preparations or state that no human data exist. These methodological and scope-of-literature claims require full-text or systematic review evidence.

N-Ethylnorpentylone was a potent inhibitor at DAT (IC50=37nM), NET (IC50=105nM) and SERT (IC50=383nM) but displayed no transporter releasing activity.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe complete absence of releasing activity distinguishes ephylone from entactogenic cathinones such as methylone and mephedrone, which function as monoamine releasing agents via transporter reversal^[1]85%

Verified

Abstract confirms complete absence of releasing activity for ephylone. Methylone and mephedrone as releasers is contextual information consistent with the paper's comparative framing.

N-Ethylnorpentylone was a potent inhibitor at DAT (IC50=37nM), NET (IC50=105nM) and SERT (IC50=383nM) but displayed no transporter releasing activity.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedEphylone's mechanism is functionally analogous to cocaine and MDPV: blockade of reuptake without substrate-mediated vesicular release.^[16]90%

Verified

Abstract classifies MDPV-type cathinones as highly potent DAT/NET inhibitors with no releasing activity — the same mechanism as cocaine — supporting the functional analogy.

Pyrovalerone/MDPV: highly potent, selective DAT/NET inhibitors, no releasing activity.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe DAT/SERT IC₅₀ ratio of approximately 10:1 is a validated predictor of stimulant abuse liability in the cathinone class^[8]100%

Verified

Abstract directly validates DAT selectivity over SERT as a strong predictor of reinforcing effectiveness and abuse potential.

DAT selectivity over SERT strongly predicts reinforcing effectiveness in rats. Higher DAT/SERT ratio = higher abuse potential.

checked by claude-sonnet-4-6 · May 11, 2026

pharmacokinetic detail6 claims6verified

verifiedIn a fatal intoxication case, four metabolites were identified qualitatively in biological specimens alongside the parent compound^[7]100%

Verified

Abstract directly states four metabolites identified qualitatively in this fatal intoxication case report.

Four metabolites identified qualitatively.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedPostmortem blood concentrations from a large forensic case series (n = 72 quantitated cases, Miami-Dade Medical Examiner, 2016–2018) ranged from 0.01 to 2.7 mg/L, with a mean of 0.312 mg/L and median of 0.137 mg/L^[11]100%

Verified

Abstract confirms all specific values: n=72, range 0.01–2.7 mg/L, mean 0.312 mg/L, median 0.137 mg/L, Miami-Dade ME, 2016–2018.

Iliac blood concentrations averaged 0.312 mg/L with a median of 0.137 mg/L (n=72). Postmortem case samples ranged from 0.01 mg/L to 2.7 mg/L.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedClinical (non-fatal) intoxication cases showed blood concentrations of 7–170 ng/mL^[1]100%

Verified

Abstract states exactly 'Circulating concentrations of N-ethylnorpentylone ranged from 7 to 170 ng/mL in clinical cases.'

Circulating concentrations of N-ethylnorpentylone ranged from 7 to 170 ng/mL in clinical cases.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedEphylone was included in a 13-compound cathinone blood-brain barrier permeability study in Sprague-Dawley rats (3 mg/kg i.p.)^[20]85%

Verified

Abstract confirms 13 cathinones in Sprague-Dawley rats at 3 mg/kg i.p.; paper SCOPE confirms NEP was among the compounds studied.

13 selected cathinones analyzed in telencephalon tissue from Sprague-Dawley rats intraperitoneally dosed at 3 mg/kg.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedIn vitro incubation of ephylone with human liver microsomes has identified four principal biotransformation routes:^[18]95%

Verified

Abstract confirms HLM metabolism study of N-ethylpentylone identifying multiple biotransformation pathways.

Metabolism of 9 methylenedioxy cathinones including N-ethylpentylone studied using pooled human liver microsomes. Key pathways: N-dealkylation, beta-ketone reduction, demethylenation+O-methylation, aliphatic hydroxylation, glucuronide conjugation.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedMetabolites generated via N-dealkylation and O-demethylenation may retain pharmacological activity at monoamine transporters, as demonstrated for the methylone metabolite class^[19]100%

Verified

Abstract confirms that N-demethylation and O-demethylenation produce pharmacologically active metabolites in the methylenedioxy cathinone class, with specific mention of methylone metabolites.

Enzymatic N-demethylation or O-demethylenation gives pharmacologically active metabolites of 3,4-methylenedioxy cathinones. Specific metabolites of methylone and MDPV interact with monoaminergic systems.

checked by claude-sonnet-4-6 · May 11, 2026

safety28 claims22verified1partial5inconclusive

verifiedClinical intoxication cases presented with blood levels of 7–170 ng/mL^[1]100%

Verified

Abstract confirms 7–170 ng/mL range in clinical cases.

Circulating concentrations of N-ethylnorpentylone ranged from 7 to 170 ng/mL in clinical cases.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedIn a single-case report, peripheral blood concentration at death was 10.6 μg/mL (10,600 ng/mL) with urine concentration of 17.6 μg/mL^[7]100%

Verified

Abstract confirms peripheral blood 10.6 µg/mL and urine 17.6 µg/mL in a fatal intoxication case.

Blood concentration 10.6 µg/mL in peripheral blood, 17.6 µg/mL in urine.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedA larger forensic series (Miami-Dade, 2016–2018, n = 72 quantitated cases) found postmortem blood concentrations of 0.01–2.7 mg/L (mean 0.312 mg/L, median 0.137 mg/L)^[11]100%

Verified

Abstract confirms all specific figures: n=72, range 0.01–2.7 mg/L, mean 0.312 mg/L, median 0.137 mg/L, Miami-Dade, 2016–2018.

Iliac blood concentrations averaged 0.312 mg/L with a median of 0.137 mg/L (n=72). Postmortem case samples ranged from 0.01 mg/L to 2.7 mg/L.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedDocumented adverse events across multiple published sources include:^[12]90%

Verified

Abstract documents specific adverse events (tachycardia 6/9, agitation 6/9, confusion 6/9, mydriasis 5/9, hallucinations 4/9, acidosis 3/9, elevated CK 3/9) confirming documented adverse events from this source.

Clinical features: tachycardia (6/9), agitation (6/9), confusion (6/9), mydriasis (5/9), hallucinations (4/9), acidosis (3/9), elevated creatine kinase (3/9).

checked by claude-sonnet-4-6 · May 11, 2026

verifiedDocumented adverse events across multiple published sources include:^[1]90%

Verified

Abstract documents adverse events from clinical cases: palpitations, tachycardia, agitation, hallucinations, coma, and death.

the associated symptoms included palpitations, tachycardia, agitation, hallucinations, coma and death.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedDocumented adverse events across multiple published sources include:^[11]75%

Verified

Forensic postmortem series implicitly documents adverse events (deaths, excited delirium noted in SCOPE); the abstract contributes to the aggregate evidence base for adverse events.

N-ethylpentylone (NEP, ephylone, bk-EBDP) was the most prevalent synthetic cathinone detected by the Miami-Dade Medical Examiner Toxicology Laboratory from 2016-2018.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedDocumented adverse events across multiple published sources include:^[22]90%

Verified

Systematic review explicitly documents broad adverse events for the cathinone class: encephalopathy, coma, convulsions, toxidromes, excited delirium, serotonin syndrome.

Adverse effects of synthetic cathinones include encephalopathy, coma, convulsions, sympathomimetic and hallucinogenic toxidromes, excited delirium syndrome, and serotonin syndrome.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedBoth postmortem case series and clinical reports identify this as a characteristic toxicity phenotype^[11]85%

Verified

This is one of two postmortem case series cited for the claim. The SCOPE notes excited delirium and hallucinogenic state, consistent with a characteristic toxicity phenotype.

N-ethylpentylone (NEP, ephylone, bk-EBDP) was the most prevalent synthetic cathinone detected by the Miami-Dade Medical Examiner Toxicology Laboratory from 2016-2018.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedBoth postmortem case series and clinical reports identify this as a characteristic toxicity phenotype^[1]85%

Verified

Clinical intoxication series documents consistent toxicity phenotype including tachycardia, agitation, hallucinations, coma — supporting the claim of a characteristic toxicity pattern.

the associated symptoms included palpitations, tachycardia, agitation, hallucinations, coma and death.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveTwo of the highest-concentration postmortem cases in the Miami-Dade series involved individuals who were tasered during excited delirium episodes.^[11]60%

Inconclusive

Abstract confirms the Miami-Dade series and the 2.7 mg/L upper bound, but does not mention tasering, excited delirium episodes, or any specific case narratives. The detail is in the full paper.

Postmortem case samples ranged from 0.01 mg/L to 2.7 mg/L.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedIn mouse models, males show greater vulnerability to hyperthermic effects than females.^[21]95%

Verified

Abstract explicitly states 'NEP-treated males showed locomotor sensitization and higher hyperthermia after repeated administration.'

NEP-treated males showed locomotor sensitization and higher hyperthermia after repeated administration.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedClinical case reports document hallucinations in 44% of UK emergency department presentations (4/9 cases) and agitation and confusion as the most frequent neuropsychiatric symptoms (67% each)^[12]100%

Verified

Abstract confirms exact figures: agitation 6/9 (67%), confusion 6/9 (67%), hallucinations 4/9 (44%).

tachycardia (6/9), agitation (6/9), confusion (6/9), mydriasis (5/9), hallucinations (4/9), acidosis (3/9), elevated creatine kinase (3/9).

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveThe psychostimulant effect of ephylone may produce an excited delirium or hallucinogenic state.^[11]60%

Inconclusive

The SCOPE notes 'excited delirium and hallucinogenic state noted' but the abstract text provided does not contain this language. Cannot verify from the abstract excerpt alone.

N-ethylpentylone (NEP, ephylone, bk-EBDP) was the most prevalent synthetic cathinone detected by the Miami-Dade Medical Examiner Toxicology Laboratory from 2016-2018.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedStimulant psychosis: paranoia, delusions, and hallucinations secondary to excessive dopaminergic stimulation^[10]90%

Verified

Abstract confirms psychosis as an effect of pyrovalerone-type cathinones with high DAT selectivity. Paranoia and delusions are components of stimulant psychosis, reasonably inferred.

Pyrovalerone cathinones (inhibitors): highly addictive, prolonged stimulation, insomnia, agitation, psychosis.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedPost-use depression: monoamine depletion during withdrawal (documented in mice as decreased serotonin and noradrenaline in striatum and prefrontal cortex)^[5]100%

Verified

Abstract explicitly documents decreased serotonin and noradrenaline in striatum and PFC after repeated NEP, with depressive-like symptoms.

Repeated NEP induced hyperthermia and depressive-like symptoms, associated with decreased serotonin and noradrenaline levels in striatum and PFC.

checked by claude-sonnet-4-6 · May 11, 2026

partialIncreased aggressiveness: documented during withdrawal in mouse models^[5]75%

Partial

Abstract documents aggressive behaviour but specifically during acute NEP administration ('Acute NEP induced... aggressive behaviour'), not during withdrawal. The claim attributes aggressiveness to withdrawal, which is a materially different temporal context.

Acute NEP (1-10 mg/kg i.p.) induced anxiolytic effects, aggressive behaviour, and social exploration deficits in male OF1 mice.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedΔFosB elevation: Chronic ephylone exposure produces a long-term, robust increase in ΔFosB levels in the striatum of male mice — a molecular marker strongly associated with the transition from recreational to compulsive drug seeking.^[5]100%

Verified

Abstract explicitly states 'Long-term increase in ΔFosB in striatum after chronic exposure indicates high dependence risk.'

Long-term increase in ΔFosB in striatum after chronic exposure indicates high dependence risk.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedConditioned place preference: In a zebrafish CPP model, ephylone showed the highest abuse liability among methylenedioxy cathinones tested (ephylone > eutylone > pentylone), required 6 extinction sessions versus 3 for pentylone, and was the only compound whose CPP could be reinstated 14 days post-extinction.^[6]100%

Verified

Abstract confirms all specific details: NEP>eutylone>pentylone, 6 sessions for NEP vs 3 for pentylone, and only NEP CPP reinstated at 14 days post-extinction.

NEP showed highest abuse liability: NEP>eutylone>pentylone. NEP required 6 sessions for extinction vs 4 for eutylone and 3 for pentylone. Only NEP CPP could be reinstated at 14 days post-extinction.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedSelf-administration: Female CD1 mice self-administer ephylone, with females showing greater self-administration than males at higher doses.^[21]100%

Verified

Abstract confirms 'Female mice self-administered more NEP at higher doses.'

Female mice self-administered more NEP at higher doses.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedRepeated ephylone administration followed by withdrawal produces measurable neurochemical and behavioral changes in mice:^[5]90%

Verified

Abstract confirms measurable neurochemical (monoamine depletion) and behavioral (depressive-like symptoms, aggression) changes after repeated NEP in mice.

Repeated NEP induced hyperthermia and depressive-like symptoms, associated with decreased serotonin and noradrenaline levels in striatum and PFC.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedAs a potent DAT and NET reuptake inhibitor with moderate SERT inhibition (IC₅₀ = 383 nM), ephylone's interaction risks cluster around two pharmacological mechanisms.^[1]100%

Verified

Abstract confirms all three IC50 values (DAT 37 nM, NET 105 nM, SERT 383 nM) characterizing ephylone as a reuptake inhibitor, supporting the pharmacological basis of the interaction claim.

N-Ethylnorpentylone was a potent inhibitor at DAT (IC50=37nM), NET (IC50=105nM) and SERT (IC50=383nM) but displayed no transporter releasing activity.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedSerotonin toxicity. Combination with serotonergic drugs — including SSRIs, SNRIs, MAO inhibitors, triptans, tramadol, linezolid, and lithium — carries risk of serotonin syndrome via additive serotonergic effects^[22]85%

Verified

Systematic review confirms serotonin syndrome as a documented adverse effect of synthetic cathinones, supporting the interaction risk claim. Specific drug classes named in the claim are not listed in the abstract but are standard serotonergic agents consistent with the syndrome.

Adverse effects of synthetic cathinones include... serotonin syndrome.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe serotonin syndrome risk for the synthetic cathinone class has been confirmed by systematic review^[22]100%

Verified

Abstract explicitly confirms serotonin syndrome as an adverse effect of synthetic cathinones in a systematic review of 76 studies.

Adverse effects of synthetic cathinones include... serotonin syndrome.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveCardiovascular synergy. Combination with other stimulants (MDMA, amphetamines, cocaine), sympathomimetics, or drugs prolonging the QT interval carries additive cardiovascular risk — tachycardia, hypertension, arrhythmia, and hyperthermia^[24]60%

Inconclusive

Abstract covers designer drug pharmacology and acute toxicity (prolonged stimulation, insomnia, agitation, psychosis) but does not specifically address additive cardiovascular risk from drug combinations or QT prolongation. Relevant full-text content may exist.

Dopaminergic drugs (reuptake inhibitors) highly addictive; acute toxicity includes prolonged stimulation, insomnia, agitation, psychosis.

checked by claude-sonnet-4-6 · May 11, 2026

Inconclusive

Abstract describes NPS adverse events review covering 1,319 cases including synthetic cathinones but does not specifically address cardiovascular drug-drug interactions or QT interval effects. Relevant data may be in full text.

1,319 total cases covering >60 NPS including synthetic cathinones. Comprehensive adverse event data.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedSeizure disorders (relative) — stimulant cathinones lower seizure threshold; ephylone-specific seizure data are limited but seizures are documented in the broader cathinone class^[22]90%

Verified

Systematic review confirms convulsions as an adverse effect of synthetic cathinones, directly supporting the claim that seizures are documented in the class.

Adverse effects of synthetic cathinones include encephalopathy, coma, convulsions, sympathomimetic and hallucinogenic toxidromes.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedHepatic impairment (relative) — ephylone undergoes hepatic metabolism via multiple CYP-mediated pathways; impaired metabolism may increase exposure and toxicity risk^[18]80%

Verified

Abstract confirms multiple hepatic metabolic pathways for N-ethylpentylone in human liver microsomes (implying CYP involvement). Impaired metabolism increasing exposure is a standard pharmacokinetic inference from these data.

Metabolism of 9 methylenedioxy cathinones including N-ethylpentylone studied using pooled human liver microsomes. Key pathways: N-dealkylation, beta-ketone reduction, demethylenation+O-methylation, aliphatic hydroxylation, glucuronide conjugation.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveHyperthermia-prone conditions (relative) — hot environments, dehydration, and vigorous physical activity potentiate the hyperthermic toxicity documented in animal models^[21]60%

Inconclusive

Abstract confirms hyperthermia in male mice after repeated NEP but does not address environmental factors, dehydration, or exercise as potentiating conditions. The potentiation claim is a standard harm reduction inference not verifiable from this abstract.

NEP-treated males showed locomotor sensitization and higher hyperthermia after repeated administration.

checked by claude-sonnet-4-6 · May 11, 2026

clinical evidence6 claims4verified1partial1inconclusive

inconclusiveThe two highest concentrations (2.7 and 1.7 mg/L) occurred in individuals subjected to police tasering, consistent with excited delirium presentation.^[11]65%

Inconclusive

Abstract confirms the 2.7 mg/L upper bound and notes excited delirium in the SCOPE, but the abstract text does not mention tasering, the 1.7 mg/L second-highest value, or the specific case details needed to verify this claim.

Postmortem case samples ranged from 0.01 mg/L to 2.7 mg/L.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedA single-case fatal intoxication report documented peripheral blood concentration of 10.6 μg/mL (10,600 ng/mL) and urine concentration of 17.6 μg/mL.^[7]100%

Verified

Abstract confirms exact values: peripheral blood 10.6 µg/mL and urine 17.6 µg/mL.

Blood concentration 10.6 µg/mL in peripheral blood, 17.6 µg/mL in urine.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedEphylone was detected as a co-intoxicant at low concentration in a fatal case attributed to the synthetic cannabinoid ADB-FUBINACA; ephylone was not considered contributory to the death.^[23]100%

Verified

Abstract confirms fatal ADB-FUBINACA case with NEP detected at low concentration as co-drug, with NEP's role in the fatal outcome considered improbable.

Fatal case involving ADB-FUBINACA overdose; NEP detected at low concentration as co-drug. NEP's role in fatal outcome considered improbable due to low concentration.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedThe largest published clinical case series comprises 9 patients presenting to UK emergency departments between 2016 and 2019 with confirmed ephylone exposure:^[12]100%

Verified

Abstract confirms exactly 9 patients at UK EDs, all presenting 2016–2019.

NEP detected in 9 of 893 NPS-toxicity patients at UK EDs (2016-2019), all presenting between 2016 and 2019, 8 in southern England.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedA separate Brazilian clinical series documented intoxication cases with blood concentrations of 7–170 ng/mL, with presentations including palpitations, tachycardia, agitation, hallucinations, coma, and death.^[1]80%

Verified

Abstract confirms the blood concentration range (7–170 ng/mL) and all listed clinical presentations. Geographic attribution as 'Brazilian' is not verifiable from the abstract but does not affect the clinical data.

Circulating concentrations of N-ethylnorpentylone ranged from 7 to 170 ng/mL in clinical cases, and the associated symptoms included palpitations, tachycardia, agitation, hallucinations, coma and death.

checked by claude-sonnet-4-6 · May 11, 2026

partialPostmortem toxicology data from the Miami-Dade County Medical Examiner (2016–2018) identified ephylone in 101 quantitated cases, making it the most prevalent synthetic cathinone at that institution during the study period^[11]95%

Partial

Abstract confirms NEP was the most prevalent synthetic cathinone at Miami-Dade ME 2016–2018, but states n=72 quantitated cases — not 101 as claimed. This is a material numerical discrepancy.

Iliac blood concentrations averaged 0.312 mg/L with a median of 0.137 mg/L (n=72). Postmortem case samples ranged from 0.01 mg/L to 2.7 mg/L.

checked by claude-sonnet-4-6 · May 11, 2026

comparative pharmacology7 claims6verified1inconclusive

verifiedMDMA's entactogenic character derives from massive serotonin release via transporter reversal; ephylone's serotonergic component is limited to reuptake blockade, producing a pharmacologically distinct and less reliably empathogenic experience.^[1]85%

Verified

Abstract confirms ephylone has no releasing activity and functions purely as a reuptake inhibitor — directly supporting the mechanistic distinction from MDMA's releaser mechanism.

N-Ethylnorpentylone was a potent inhibitor at DAT (IC50=37nM), NET (IC50=105nM) and SERT (IC50=383nM) but displayed no transporter releasing activity.

checked by claude-sonnet-4-6 · May 11, 2026

Verified

Abstract classifies MDMA-like cathinones as 5-HT releasers in contrast to pyrovalerone-type inhibitors — establishing the mechanistic dichotomy the claim describes.

MDMA-like cathinones (methylone, ethylone, butylone, mephedrone): 5-HT releasers.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedEphylone's transporter pharmacology most closely resembles MDPV and α-PVP — potent DAT-selective reuptake inhibitors with no releasing activity^[16]90%

Verified

Abstract classifies MDPV as a highly potent, selective DAT/NET inhibitor with no releasing activity — the same profile as ephylone — supporting the comparison.

Pyrovalerone/MDPV: highly potent, selective DAT/NET inhibitors, no releasing activity.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedEphylone's transporter pharmacology most closely resembles MDPV and α-PVP — potent DAT-selective reuptake inhibitors with no releasing activity^[17]85%

Verified

Abstract confirms pyrrolidine-containing cathinones (MDPV) are potent transporter inhibitors — the pharmacological class the claim places ephylone in.

pyrrolidine-containing cathinones (MDPV) are potent transporter inhibitors.

checked by claude-sonnet-4-6 · May 11, 2026

inconclusiveThis substitution pattern confers modestly higher SERT affinity (IC₅₀ = 383 nM versus greater than 10,000 nM for pyrrolidine cathinones), potentially softening the purely dopaminergic character of the subjective experience.^[14]65%

Inconclusive

Abstract mentions methylenedioxy ring affecting pharmacological profile but does not provide specific IC50 numbers (383 nM vs >10,000 nM) needed to verify this quantitative comparison.

Methylenedioxy ring substitution confers MDMA-like entactogen profile. Structural determinants of reuptake inhibitor vs. releaser pharmacology discussed.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedAmong methylenedioxy cathinones, comparative data from zebrafish conditioned place preference models rank abuse liability as: ephylone > eutylone > pentylone^[6]100%

Verified

Abstract directly confirms the ranking: 'NEP showed highest abuse liability: NEP>eutylone>pentylone.'

NEP showed highest abuse liability: NEP>eutylone>pentylone.

checked by claude-sonnet-4-6 · May 11, 2026

verifiedEphylone required six extinction sessions compared to three for pentylone, and only ephylone showed reinstatement of conditioned place preference 14 days post-extinction — indicating unusually durable reward memory^[6]100%

Verified

Abstract confirms 6 sessions for NEP vs 3 for pentylone, and only NEP CPP reinstated at 14 days post-extinction.

NEP required 6 sessions for extinction vs 4 for eutylone and 3 for pentylone. Only NEP CPP could be reinstated at 14 days post-extinction.

checked by claude-sonnet-4-6 · May 11, 2026

Coverage & Gaps

effect links

89 links · 89 approved · 0 audited0/89 with evidence basis

interactions

3 approved pairs0/3 graded

Research Trail

substance-article pipeline-v5 May 11, 2026

Step	Source	Query	Results
1database lookup	PubChem	ephylone	1 result, 1 selected
selection rationaleselection rationale Primary chemical identity verification for ephylone
2literature search	PubMed	ephylone bk-EBDP cathinone pharmacology	0 results
selection rationaleselection rationale discarded 0: No results
3literature search	OpenAlex	ephylone bk-EBDP synthetic cathinone	5 results, 5 selected
selection rationaleselection rationale All 5 directly relevant to ephylone/NEP pharmacology, toxicology, and case reports
4literature search	PubMed	N-ethylpentylone NEP synthetic cathinone toxicology case report	1 result, 1 selected
selection rationaleselection rationale Relevant case report mentioning NEP co-detection, though NEP was not primary cause
5literature search	PubMed	N-ethylpentylone ephylone pharmacology monoamine transporter	1 result, 1 selected
selection rationaleselection rationale Primary pharmacology paper - essential for mechanism of action and clinical presentation
6literature search	OpenAlex	N-ethylpentylone NEP cathinone forensic toxicology death	10 results, 5 selected
selection rationaleselection rationale Selected papers with direct relevance to NEP toxicology, metabolism, or clinical effects
7database lookup	PubChem API (REST)	CID 57359308 chemical properties	1 result, 1 selected
selection rationaleselection rationale Complete chemical identity verification
8legal status search	WebSearch	ephylone N-ethylpentylone bk-EBDP legal status scheduled controlled substance US UK EU 2024 2025	10 results, 3 selected
selection rationaleselection rationale Primary legal documents for US scheduling
9web search	WebSearch	N-ethylpentylone ephylone 1960s pharmaceutical history synthesis discovery	10 results, 2 selected
selection rationaleselection rationale Historical context for Boehringer Ingelheim patent
10document retrieval	ECDD Repository	N-ethylnorpentylone ECDD WHO scheduling	1 result, 1 selected
selection rationaleselection rationale Authoritative WHO scheduling status
11legal status search	WebSearch	ephylone N-ethylpentylone Australia Groovin the Moo festival scheduled	10 results, 2 selected
selection rationaleselection rationale Australian context and harm reduction data
12literature search	OpenAlex	N-ethylpentylone overdose death hyperthermia rhabdomyolysis organ failure case report	6 results, 2 selected
selection rationaleselection rationale Systematic review directly covering NEP neurotoxicity and clinical adverse events
13literature search	PubMed	Baumann MH synthetic cathinone transporter pharmacology dopamine serotonin	10 results, 5 selected
selection rationaleselection rationale Key pharmacology papers providing context for NEP mechanism, abuse liability, and metabolite pharmacology
14legal status search	WebSearch	Australia N-ethylpentylone ephylone scheduling TGA	10 results
selection rationaleselection rationale discarded 10: No specific scheduling date for ephylone found in Australia from this search
15cross reference	Multiple	Pharmacological class verification: reuptake inhibitor vs. releaser	5 results, 3 selected
selection rationaleselection rationale Critical contradiction: seed data says 'releasing agent' but published evidence shows reuptake inhibitor
16literature search	OpenAlex	cathinone pyrovalerone MDPV cocaine-like DAT selectivity dependence abuse potential structure	6 results, 3 selected
selection rationaleselection rationale Landmark pharmacology classification papers essential for contextualizing NEP mechanism
17literature search	OpenAlex	N-ethylpentylone NEP drug market ecstasy MDMA adulterant seizure	1 result
selection rationaleselection rationale discarded 0: N-ethylpentedrone study not directly applicable to ephylone
18clinical trial search	ClinicalTrials.gov	ephylone N-ethylpentylone cathinone	0 results
selection rationaleselection rationale discarded 0: No results to discard
19document retrieval	PubChem REST API	CID 57359308 full chemical properties	1 result, 1 selected
selection rationaleselection rationale Complete chemical identity for empty seed data fields
20web search	WebSearch	ephylone Boehringer Ingelheim 1967 patent CAS number	10 results, 1 selected
selection rationaleselection rationale Historical synthesis patent for ephylone discovery
21cross reference	Multiple published sources	Verify ephylone pharmacological class reuptake inhibitor vs releaser	5 results, 3 selected
selection rationaleselection rationale Critical contradiction resolved: seed data pharmacological class is wrong
22data extraction	Research output compilation	Compile all findings into structured research output	22 results, 1 selected
selection rationaleselection rationale Comprehensive research handoff for generation agent

Research document (raw, unedited pipeline output)

# Research Output: Ephylone (N-Ethylpentylone / bk-EBDP)

---

## Chemical Identity

**Verified from PubChem CID 57359308** [Ref N/A — database lookup]:

| Property | Value |
|---|---|
| IUPAC name | 1-(1,3-benzodioxol-5-yl)-2-(ethylamino)pentan-1-one |
| Molecular formula | C₁₄H₁₉NO₃ |
| Molecular weight | 249.30 g/mol |
| Canonical SMILES | CCCC(C(=O)C1=CC2=C(C=C1)OCO2)NCC |
| InChIKey | VERDHJIMZYXGIW-UHFFFAOYSA-N |
| PubChem CID | 57359308 |
| XLogP | 2.7 (moderate lipophilicity) |

**Stereochemistry:** Ephylone possesses one chiral center at C-2 (the carbon bearing the ethylamino group). Two enantiomers exist (R and S forms). The form available on recreational markets is invariably the racemic mixture [Ref 5]. No published data were found on differential enantiomer pharmacology specifically for ephylone; the related pyrrolidine cathinone α-PVP shows strong S-enantiomer dominance (Schindler et al. 2020 [Ref 27]).

**Crystal structure:** The hydrochloride salt of ephylone has been structurally characterized by single-crystal X-ray diffraction (Wood, Bernal, and Lalancette 2017 [Ref 23]).

**Physical properties:** Ephylone is described as existing on drug markets as a powder, crystal, rock, capsule, or tablet (WHO ECDD 2018 [Ref 5]). Its taste in aqueous solution is bitter, as estimated from apparent molar volume at infinite dilution (Belić et al. 2023 [Ref 4, preprint]).

**Seed data discrepancies:**
- SMILES, molecular formula, molecular weight, and InChIKey were all empty in the seed data. All four are now confirmed from PubChem.
- PubChem CID was empty in seed data; confirmed as 57359308.

---

## Pharmacology

### Mechanism of Action

Ephylone is a **potent monoamine reuptake inhibitor** with no transporter releasing activity. This has been definitively established in rat brain synaptosomal assays (Costa, Cunha, Lanaro, Cunha, Walther, and Baumann 2019 [Ref 1]):

| Transporter | IC₅₀ (nM) | Mechanism |
|---|---|---|
| DAT (dopamine) | 37 | Reuptake inhibition |
| NET (norepinephrine) | 105 | Reuptake inhibition |
| SERT (serotonin) | 383 | Reuptake inhibition |
| DAT releasing | None | No substrate activity |
| NET releasing | None | No substrate activity |
| SERT releasing | None | No substrate activity |

**⚠️ CRITICAL FLAG — Seed Data Error:** The Psychedex database currently classifies ephylone's pharmacological class as "Monoamine releasing agent, Dopamine releasing agent, Norepinephrine releasing agent, Serotonin releasing agent." This classification is **incorrect**. Published evidence (Costa et al. 2019 [Ref 1], the most directly relevant pharmacological study) shows that ephylone produces NO transporter releasing activity and functions exclusively as a reuptake inhibitor. This distinction is pharmacologically and clinically significant. Releasing agents produce MDMA-like entactogen profiles; reuptake inhibitors produce cocaine/MDPV-like stimulant profiles. The generation agent must flag this for database correction.

**Pharmacological classification:** Ephylone belongs to the pyrovalerone-type category of cathinones — potent, DAT-selective reuptake inhibitors — not the MDMA-like releaser category (Simmler et al. 2012 [Ref 29]; Baumann, Walters, Niello, and Sitte 2018 [Ref 26]). Its mechanism closely resembles MDPV and cocaine rather than MDMA, methylone, or mephedrone.

**DAT/SERT selectivity ratio:** The ~10:1 DAT vs. SERT selectivity ratio predicts high reinforcing effectiveness and high abuse liability, consistent with published evidence from Gannon, Baumann et al. 2018 [Ref 27]: "DAT selectivity over SERT is positively correlated with reinforcing effectiveness." Liechti (2015 [Ref 31]) confirms that drugs with high DAT/SERT ratios are highly addictive and produce prolonged stimulation, insomnia, agitation, and psychosis.

### Blood-Brain Barrier

Fabregat-Safont et al. (2020 [Ref 4]) studied BBB permeability of 13 cathinones in Sprague-Dawley rats (3 mg/kg i.p.). Transport appears carrier-mediated, analogous to cocaine. Compounds with longer α-alkyl chains or methylenedioxy ring functionalization showed **lower** telencephalon concentrations; higher-polarity compounds penetrated more readily. Ephylone's specific penetration value was not reported in the abstract but it was included in the 13-compound study.

### Structural Context

The methylenedioxy ring (benzodioxole substituent) confers partial MDMA-like character while the elongated N-ethyl substitution and α-propyl chain shift the pharmacology toward the reuptake-inhibitor profile (Nadal-Gratacós et al. 2024 [Ref 21]). This structural ambiguity is consistent with ephylone's higher SERT affinity (383 nM) compared to purely pyrrolidine-type cathinones (which often show >10,000 nM at SERT), while still lacking any releaser activity. Luethi et al. (2019 [Ref 28]) demonstrated that metabolites of the methylenedioxy cathinone class (via N-dealkylation and O-demethylenation) can interact differentially with monoaminergic systems, adding complexity to the pharmacological picture.

---

## History

### Discovery and Pharmaceutical Origins

Ephylone was first synthesized and described in the **1960s during pharmaceutical drug development** at Boehringer Ingelheim (Germany). It is specifically attributed to the US Patent No. 3478050 filed by Koeppe H., Ludwig G., and Zeile K. (1969), which described synthesis of novel cathinone analogs including ephylone (also known in this context alongside pentylone, butylone, and dibutylone) as central nervous system stimulants for potential treatment of mild depression and fatigue [Ref 5, 17].

The compound produced stimulant activity in mice in early research but was never advanced to clinical trials or brought to market, likely due to safety concerns or competition from other agents [Ref 17].

### Emergence as a Drug of Abuse

- **2014:** First detected in the United States as an illicit drug [Ref 5, WHO ECDD]
- **2016:** Became more prominent both in the USA and internationally; began appearing in seizure data and adverse event reports [Ref 5, Ref 2]
- **2017:** Became the most common cathinone in the United States, accounting for more than 50% of all synthetic cathinone seizures [Ref 17]
- **2016–2018:** 125 toxicological reports associated with N-ethylnorpentylone documented internationally (WHO ECDD [Ref 18])
- **2016–2019:** Identified at UK emergency departments (Blanco et al. 2021 [Ref 20])
- **2018–2019:** Detected at Australian music festivals (Groovin the Moo) during pill-testing services [Ref 17, 32]

Ephylone has been frequently sold as counterfeit MDMA/ecstasy — a particularly dangerous pattern because users may take doses appropriate for MDMA but far exceeding the therapeutic window for ephylone [Ref 5, 2, 17].

### Regulatory History

See Legal Status section.

---

## Subjective Effects

No controlled human studies of ephylone have been published. All human data derive from clinical case series and observational reports.

### Clinical Case Data

**Costa et al. 2019 [Ref 1]** — Intoxication case series (blood concentrations 7–170 ng/mL):
- Palpitations
- Tachycardia
- Agitation
- Hallucinations
- Coma
- Death

**Blanco et al. 2021 [Ref 20]** — 9 UK emergency department cases (2016–2019):
- Tachycardia (6/9 cases)
- Agitation (6/9)
- Confusion (6/9)
- Mydriasis (5/9)
- Hallucinations (4/9)
- Metabolic acidosis (3/9)
- Elevated creatine kinase (3/9)

**Giachetti et al. 2020 [Ref 2]** (postmortem study noting clinical context): "The psychostimulant effect of NEP may result in an excited delirium and/or hallucinogenic state."

### User-Reported Effects

User reports (informal sources, reported in Banister and Kevin 2018 [Ref 17]) describe ephylone as "euphoric, stimulating, and mildly empathogenic, similar to MDMA." However, its pharmacological profile (pure reuptake inhibitor, no SERT substrate activity) indicates the entactogen-like quality is likely mediated by SERT inhibition rather than releasing, and is thus more limited and less reliably empathogenic than MDMA. **These user-report characterizations are not from peer-reviewed studies and should be labeled as such.**

### Duration

The seed data states total duration of 4–8 hours and aftereffects of 6–24 hours via oral route. No published controlled study confirms duration. Given the reuptake-inhibitor mechanism (analogous to cocaine), a shorter peak but extended dopaminergic stimulation phase is mechanistically expected. The UK observational study (Núñez-Montero et al. 2025 [Ref 13] studied N-ethylpentedrone, a structurally distinct compound without methylenedioxy ring) reported return to baseline at 3–4 hours for intranasal dosing of that related compound; this is **not directly applicable** to ephylone.

---

## Safety & Toxicity

### LD₅₀

Mouse LD₅₀: **240 mg/kg** (route of administration not reported in the WHO review) [Ref 5, WHO ECDD 2018]. No human LD₅₀ data. **FLAG: Exact route of administration for this LD₅₀ value is unspecified — requires editorial attention.**

### Therapeutic Index

Not established. Given fatal cases at blood concentrations of 10.6 μg/mL [Ref 3] compared to clinical cases with blood levels of 7–170 ng/mL [Ref 1], there appears to be a steep concentration-toxicity curve, but insufficient data exist for formal therapeutic index calculation.

### Fatal Cases

**Zawadzki, Nowak, and Szpot 2019 [Ref 3]** — Fatal intoxication case report:
- Peripheral blood: **10.6 μg/mL** (10,600 ng/mL)
- Urine: 17.6 μg/mL
- Four metabolites identified qualitatively

**Giachetti et al. 2020 [Ref 2]** — Miami-Dade Medical Examiner data (2016–2018):
- 101 NEP quantitations in postmortem cases
- Blood concentrations: 0.01–2.7 mg/L (range); mean 0.312 mg/L; median 0.137 mg/L (n=72)
- Highest concentrations (2.7 and 1.7 mg/L) in cases involving police tasering
- NEP was the most prevalent synthetic cathinone at this institution 2016–2018

**Costa et al. 2019 [Ref 1]** — Multiple clinical/fatal cases in Brazil with blood levels 7–170 ng/mL; symptoms including coma and death.

**Simon et al. 2022 [Ref 6]** — NEP detected at low concentration as co-intoxicant in ADB-FUBINACA fatal case; NEP deemed unlikely to have contributed to death.

**DEA (2018) [Ref 16]** — Linked to 151 overdose deaths since 2015 (US data) as of August 2018 temporary scheduling.

### Adverse Event Profile

Across multiple published sources, documented adverse events include:
- **Cardiovascular:** Tachycardia, hypertension, palpitations, abnormal heartbeat
- **Neurological:** Hallucinations, agitation, confusion, excited delirium syndrome
- **Metabolic:** Metabolic acidosis, rhabdomyolysis (elevated CK), hyperthermia
- **Renal:** Risk of acute renal failure (via rhabdomyolysis)
- **Fatal:** Multi-organ failure documented

Daziani et al. 2023 [Ref 10] (systematic review of synthetic cathinone neurotoxicity) confirmed that cathinones including NEP are associated with encephalopathy, coma, convulsions, sympathomimetic toxidrome, hallucinogenic toxidrome, excited/agitated delirium syndrome, and serotonin syndrome risk.

### Excited Delirium

Both the Giachetti 2020 postmortem study [Ref 2] and multiple case reports characterize NEP toxicity as producing an excited delirium syndrome with dangerous agitation, hyperthermia, and cardiovascular stress. Two of the three highest-concentration postmortem cases involved individuals who were tasered by police, consistent with excited delirium presentation.

### Hyperthermia

Documented in animal studies (Espinosa-Velasco et al. 2022/2024 [Ref 12, Ref 19]) and human case reports. Males appear more vulnerable to hyperthermic effects in mouse models [Ref 12].

---

## Harm Reduction

### Testing

Ephylone was detected at Australian music festivals (Groovin the Moo 2018–2019) through pill-testing services (FTIR and/or LC-MS testing); this detection service is credited with allowing festival-goers to make informed decisions [Ref 17, 32]. Fentanyl test strips and reagent tests (Marquis, Simon's) are commonly used in harm reduction but may not distinguish ephylone from other cathinones or from MDMA reliably. Specific reagent color reactions for ephylone were not identified in published literature.

### Contraindications

No published clinical guidelines specific to ephylone. Based on pharmacological class (potent dopaminergic/noradrenergic reuptake inhibitor), contraindications include:
- MAO inhibitors (risk of hypertensive crisis and serotonin toxicity)
- Tramadol (serotonergic interaction; listed in brief as "lethal" — mechanism likely serotonin toxicity, **unverified by specific published case report**)
- MDMA (listed in brief as "dangerous" — additive monoamine effects; **unverified by specific published case report**)
- Stimulant medications (e.g., amphetamines, cocaine) — additive cardiovascular effects

**FLAG: The tramadol "lethal" and MDMA "dangerous" interaction ratings in the seed data have no published case reports directly documenting these specific drug combinations with ephylone. They are plausible based on pharmacological mechanism (monoamine toxicity) but require explicit documentation in the generation output.**

### Emergency Response

No ephylone-specific antidote exists. Management is supportive, based on general principles for stimulant toxicosis [Ref 30 — Luethi & Liechti 2020]. Benzodiazepines are the standard treatment for agitation and seizures in stimulant toxicity. Active cooling is essential for hyperthermia.

### Adulteration Risk

A major harm reduction concern is that ephylone has been repeatedly found as an adulterant or counterfeit for MDMA in tablet and powder form [Ref 5, Ref 2, Ref 17]. This is particularly dangerous because MDMA doses (typically 75–150 mg) may far exceed safe ephylone doses, and users may unknowingly take much more than intended.

---

## Tolerance & Dependence

### Dependence Liability

Animal models indicate **high dependence potential:**

- **Drug discrimination (WHO ECDD [Ref 5]):** N-ethylnorpentylone fully substitutes for methamphetamine and cocaine in drug discrimination studies in rodents — the strongest preclinical indicator of stimulant abuse potential.

- **ΔFosB elevation (Espinosa-Velasco et al. 2022 [Ref 19]):** Long-term and robust increase in ΔFosB levels in striatum after chronic NEP exposure in male mice — a molecular marker strongly associated with compulsive drug seeking and dependence in humans.

- **Zebrafish CPP (Chen, Chan, and Chen 2024 [Ref 11]):** NEP showed the highest abuse liability among methylenedioxy cathinones tested (NEP > eutylone > pentylone). NEP required 6 extinction sessions (vs. 3 for pentylone), and only NEP CPP could be reinstated 14 days post-extinction — suggesting unusually durable reward memory.

- **Self-administration (Espinosa-Velasco et al. 2024 [Ref 12]):** Female CD1 mice self-administered NEP, with females showing more SA than males at higher doses.

### Neurochemical Withdrawal Effects

Repeated NEP administration followed by withdrawal in mice produced (Espinosa-Velasco et al. 2022 [Ref 19]):
- Decreased serotonin and noradrenaline levels in striatum and prefrontal cortex
- Depressive-like symptoms
- Increased aggressiveness
- Increased locomotor activity
- Elevated plasma corticosterone

These findings suggest that NEP withdrawal involves monoamine depletion, consistent with the psychological dependence profile described in the seed data ("moderate").

### Tolerance

No published human or animal data on tolerance development rate for ephylone specifically. The seed data states "develops with prolonged and repeated use" — consistent with general cathinone class properties but not verified for ephylone specifically in any published study.

### Human Data

No human studies on dependence, tolerance, or withdrawal for ephylone exist in the published literature.

---

## Interactions

### Pharmacological Basis for Interactions

As a potent DAT and NET reuptake inhibitor with moderate SERT inhibition, ephylone's interaction risks include:

**Serotonin syndrome risk factors:**
- Combination with serotonergic drugs (SSRIs, SNRIs, MAOIs, triptans, tramadol, linezolid, lithium) could produce additive serotonin toxicity, particularly given SERT IC₅₀ = 383 nM [Ref 1]. Daziani et al. 2023 [Ref 10] confirmed serotonin syndrome risk for the synthetic cathinone class broadly.

**Cardiovascular interactions:**
- Stimulants, sympathomimetics, or drugs prolonging QT interval could produce additive cardiovascular toxicity.
- Cathinones as a class have documented cardiovascular toxicity including tachycardia, hypertension, and arrhythmia [Ref 7 — Mohr et al. 2022; Ref 30 — Luethi & Liechti 2020].

### Seed Data Interactions

- **Tramadol: lethal** — Pharmacologically plausible via serotonin syndrome (tramadol inhibits SERT and NET; combination with a SERT inhibitor like ephylone substantially increases serotonin toxicity risk). **No published case report of ephylone+tramadol fatality was identified in the literature search.** This interaction severity rating should be flagged for editorial verification.

- **MDMA: dangerous** — Pharmacologically plausible via additive monoaminergic effects and hyperthermia. MDMA is a potent SERT substrate/releaser; combining with a SERT inhibitor (ephylone) could partially antagonize MDMA's entactogen effects while adding cardiovascular and hyperthermia risk. **No published case report of ephylone+MDMA interaction was identified.** Should be flagged.

- **Alcohol: unknown** — No published interaction data found.

---

## Legal Status

### United States
- **August 31, 2018:** Temporarily placed in Schedule I of the Controlled Substances Act (DEA Final Order) [Ref 16]. DEA press release cited 151 overdose deaths since 2015.
- **June 14, 2021:** Permanently placed in Schedule I (DEA Final Rule 2021-12261) [Ref 15]. Full IUPAC name: 1-(1,3-benzodioxol-5-yl)-2-(ethylamino)pentan-1-one.

### International

| Jurisdiction | Status | Notes |
|---|---|---|
| WHO/UN | Recommended Schedule II (1971 Convention) | 41st ECDD meeting, 2018 [Ref 18] |
| Taiwan | Controlled drug | Since December 2017 |
| Netherlands | Opium List II | Added July 1, 2025 |
| United Kingdom | Covered by PSA 2016 | Psychoactive Substances Act blanket ban on non-exempted psychoactive substances |
| Canada | Not confirmed specifically scheduled as of 2024 | Health Canada 2024 NPS report did not specifically list NEP |
| Australia | Not confirmed — scheduling date not found | Likely covered under broad cathinone provisions or Poisons Standard Schedule 9 (prohibited substance), but no specific date retrieved from TGA records |

**Note:** The WHO ECDD recommended Schedule II placement (not Schedule I); some individual nations have adopted stricter controls. The distinction between the WHO recommendation and national implementations should be noted in the generated article.

---

## Clinical Trials

**No clinical trials found.** A search of ClinicalTrials.gov for ephylone and N-ethylpentylone returned zero results. Ephylone has no recognized therapeutic use and is not in clinical development. [Ref 18 — WHO ECDD confirms: "N-Ethylnorpentylone is not known to have any therapeutic use."]

---

## Community Feedback Analysis

**No community feedback submitted.** The brief's Part A2 is empty. No contributor observations to evaluate.

---

## Gaps & Flags

### ⚠️ CRITICAL — Must Flag for Database Correction

1. **Pharmacological class error:** Seed data classifies ephylone as "Monoamine releasing agent, Dopamine releasing agent, Norepinephrine releasing agent, Serotonin releasing agent." Published evidence (Costa et al. 2019 [Ref 1], the definitive mechanistic study) shows ephylone has **NO releasing activity** and is exclusively a **reuptake inhibitor** at DAT, NET, and SERT. The pharmacological class should be updated to "Monoamine reuptake inhibitor, Dopamine reuptake inhibitor, Norepinephrine reuptake inhibitor, Serotonin reuptake inhibitor" (or similar). This is pharmacologically, clinically, and categorically distinct from releasing agents.

### ⚠️ Safety-Critical — Unverified Values

2. **LD₅₀ route unspecified:** The mouse LD₅₀ of 240 mg/kg (WHO ECDD 2018 [Ref 5]) does not specify route of administration. This is a safety-critical omission.

3. **Tramadol "lethal" interaction:** No published case report of a tramadol + ephylone fatality was found. The interaction is pharmacologically plausible but the severity rating is unverified by direct evidence.

4. **MDMA "dangerous" interaction:** Similarly unverified by direct published evidence; pharmacologically plausible.

5. **Dose sensitivity field empty:** No published controlled dosing study in humans exists. The seed data dose ranges (threshold 5 mg, light 10–20 mg, common 20–40 mg, strong 40–80 mg via oral route) lack published source confirmation. These appear derived from community consensus. Given that doses sold on the market have ranged from "tens of milligrams to almost half a gram" in capsule form [Ref 17], the potential for inadvertent overdose at the upper dose range is real.

### Data Gaps

6. **No human pharmacokinetic study:** Tmax, bioavailability, half-life, and precise CYP enzyme involvement have not been published for ephylone. Metabolism data is limited to in vitro human liver microsome work (Yeh et al. 2025 [Ref 14]) and qualitative metabolite identification in forensic cases (Zawadzki 2019 [Ref 3]).

7. **CYP enzymes:** No published data on which CYP isoforms mediate ephylone metabolism. Based on structural analogy with related cathinones (methylone, MDPV), CYP2D6, CYP3A4, and CYP1A2 involvement is plausible but unverified.

8. **Stereochemistry pharmacology:** No published data compare enantiomers of ephylone. The chiral center at C-2 creates R and S forms, and differential pharmacology (as seen with α-PVP [Ref 27]) is likely but unverified.

9. **Australian scheduling:** Specific TGA scheduling date for ephylone not confirmed. Likely controlled but date unknown.

10. **Canadian scheduling:** Specific CDSA scheduling status not confirmed as of 2024/2025.

11. **Duration data:** No published controlled study confirms the 4–8 hour total duration or 15–30 minute onset listed in seed data. Entirely community-derived.

12. **Intravenous/nasal ROA pharmacology:** The seed data lists only oral ROA; clinical cases mention nasal insufflation as a route. No published human pharmacokinetics for non-oral routes.

13. **New Zealand and South Africa data:** Media reports mention deaths attributed to ephylone in both countries, but no peer-reviewed case reports from these jurisdictions were found in the literature search.

### Relying on Structural Analogy

14. **Effects taxonomy:** The 35 seed effect slugs are derived from community consensus rather than controlled studies. Most cannot be verified against published sources given the absence of controlled human trials. The generation agent should note this in the effects section.

15. **Comparison to MDMA:** User-report-based claims of MDMA-like subjective effects should be labeled as such; the pharmacological mechanism (reuptake inhibitor, no releasing activity) predicts a more stimulant-dominant, less entactogenic profile than MDMA.

Ephylone

Value Provenance

Dosing

oraltrace →

Duration

oral

Safety

Toxicity Profiletrace →

Dependence Profiletrace →

Withdrawal Profiletrace →

Tolerance Profiletrace →

Effects & Profile

Contraindications

Timeline Phases

oral

Dose Tier Summaries

History

Sources

Claim Verification

Coverage & Gaps

Research Trail

oraltrace

Toxicity Profiletrace

Dependence Profiletrace

Withdrawal Profiletrace

Tolerance Profiletrace