Prolintane

Sources

6 strong · 9 moderate · 11 weak

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

Claims checked

64verified15partial4inconclusive7not supported

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

Generated

May 13, 2026 · pipeline-v5

Values approved

83/84 (99%)

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	15–25 mg	15–25 mg	low
Common	25–45 mg	25–45 mg	low
Strong	45–60 mg	45–60 mg	low
Heavy	60+ mg	60+ mg	low
Editorial	Values carried forward from existing DB / PsychonautWiki community consensus. No controlled human dose-response study with pharmacokinetic monitoring exists. Controlled human studies (Kuitunen 1984, Nicholson 1980) used 5-30 mg for therapeutic/sleep effects, confirming activity in the light-to-common range. Katovit tablets contained 200 mg — far above the heavy threshold, suggesting tolerance in chronic users. Community-derived ranges are plausible but pharmacokinetically unverified.
	ReasoningReasoning Values carried forward from existing DB / PsychonautWiki community consensus. No controlled human dose-response study with pharmacokinetic monitoring exists. Controlled human studies (Kuitunen 1984, Nicholson 1980) used 5-30 mg for therapeutic/sleep effects, confirming activity in the light-to-common range. Katovit tablets contained 200 mg — far above the heavy threshold, suggesting tolerance in chronic users. Community-derived ranges are plausible but pharmacokinetically unverified. Evidence basis: community_consensus_large

Duration

oral

Field	Published	AI Proposed	Confidence
Come uptrace	20–40 minutes	20–40 minutes	low
Editorial	Community consensus (PsychonautWiki). No controlled PK data to confirm. Pharmacodynamically plausible given peak effects at 2-3 hours.
	ReasoningReasoning Community consensus (PsychonautWiki). No controlled PK data to confirm. Pharmacodynamically plausible given peak effects at 2-3 hours. Evidence basis: community_consensus_large
After effectstrace	2–6 hours	2–6 hours	low
Editorial	Community consensus (PsychonautWiki). Extended aftereffect period expected from NDRI mechanism — residual catecholamine rebalancing. No controlled data.
	ReasoningReasoning Community consensus (PsychonautWiki). Extended aftereffect period expected from NDRI mechanism — residual catecholamine rebalancing. No controlled data. Evidence basis: community_consensus_large
Onsettrace	20–60 minutes	20–60 minutes	low
Editorial	Community consensus (PsychonautWiki). No human PK data. Consistent with pharmacodynamic timecourse — cognitive enhancement peaks at ~2.5h post-dose (Kuitunen 1984), implying onset well before 1 hour.
	ReasoningReasoning Community consensus (PsychonautWiki). No human PK data. Consistent with pharmacodynamic timecourse — cognitive enhancement peaks at ~2.5h post-dose (Kuitunen 1984), implying onset well before 1 hour. Evidence basis: community_consensus_large
Peaktrace	2–3 hours	2–3 hours	low
Editorial	Community consensus (PsychonautWiki). Supported by pharmacodynamic data: cognitive enhancement at 2.5h post-dose (Kuitunen 1984) and REM suppression concentrated in first 2h of post-dose sleep (Nicholson 1980).
	ReasoningReasoning Community consensus (PsychonautWiki). Supported by pharmacodynamic data: cognitive enhancement at 2.5h post-dose (Kuitunen 1984) and REM suppression concentrated in first 2h of post-dose sleep (Nicholson 1980). Evidence basis: community_consensus_large
Offsettrace	1–2 hours	1–2 hours	low
Editorial	Community consensus (PsychonautWiki). No controlled PK data. Consistent with total duration of 4-6 hours.
	ReasoningReasoning Community consensus (PsychonautWiki). No controlled PK data. Consistent with total duration of 4-6 hours. Evidence basis: community_consensus_large
Totaltrace	4–6 hours	4–6 hours	low
Editorial	Community consensus (PsychonautWiki). Consistent with pharmacodynamic timecourse from controlled studies (cognitive peak at 2.5h, REM suppression in first 2h of sleep). No plasma concentration data to confirm.
	ReasoningReasoning Community consensus (PsychonautWiki). Consistent with pharmacodynamic timecourse from controlled studies (cognitive peak at 2.5h, REM suppression in first 2h of sleep). No plasma concentration data to confirm. Evidence basis: community_consensus_large

Safety

Toxicity Profiletrace

Field	Published	AI Proposed	Confidence
Acute	moderate	moderate	low
Chronic	moderate	moderate	low
Organs Affected	cardiovascular, neurological	cardiovascular, neurological	low
Editorial	Both acute and chronic ratings are class-inferred, not substance-confirmed. The strongest substance-specific signals are rodent hERG inhibition/QT prolongation (Jeong 2023, cardiovascular) and rodent microglial activation (Jeong 2023, neurological). Overdose deaths in polydrug context (Kyle 2007) prevent isolation of prolintane's contribution. No human toxicity studies exist.
	ReasoningReasoning Both acute and chronic ratings are class-inferred, not substance-confirmed. The strongest substance-specific signals are rodent hERG inhibition/QT prolongation (Jeong 2023, cardiovascular) and rodent microglial activation (Jeong 2023, neurological). Overdose deaths in polydrug context (Kyle 2007) prevent isolation of prolintane's contribution. No human toxicity studies exist. Evidence basis: animal_study

Dependence Profiletrace

Field	Published	AI Proposed	Confidence
Physical	low	low	low
Psychological	moderate	moderate	low
Compulsive Redosing	moderate	moderate	low
Dose Escalation	moderate	moderate	low
Editorial	All dependence data derive from rodent behavioral pharmacology (Lee 2022). No human dependence or withdrawal studies exist. Physical dependence rated low (no documented physical withdrawal); psychological dependence rated moderate based on rodent self-administration and conditioned place preference plus historical market withdrawal for abuse liability.
	ReasoningReasoning All dependence data derive from rodent behavioral pharmacology (Lee 2022). No human dependence or withdrawal studies exist. Physical dependence rated low (no documented physical withdrawal); psychological dependence rated moderate based on rodent self-administration and conditioned place preference plus historical market withdrawal for abuse liability. Evidence basis: animal_study

Withdrawal Profiletrace

Field	Published	AI Proposed	Confidence
Severity	mild	mild	low
Symptoms	fatigue, anhedonia, dysphoria, hypersomnia, increased appetite	fatigue, anhedonia, dysphoria, hypersomnia, increased appetite	low
Fatal	No	No	low
Medical Supervision	Not required	Not required	low
Editorial	No substance-specific withdrawal data exist. Withdrawal profile inferred entirely from cocaine and methylphenidate class analogy — expected post-use dopaminergic deficit states. Timing estimates are class-level approximations from NDRI stimulant withdrawal literature.
	ReasoningReasoning No substance-specific withdrawal data exist. Withdrawal profile inferred entirely from cocaine and methylphenidate class analogy — expected post-use dopaminergic deficit states. Timing estimates are class-level approximations from NDRI stimulant withdrawal literature. Evidence basis: animal_study

Tolerance Profiletrace

Field	Published	AI Proposed	Confidence
Buildup	moderate	moderate	low
Half-life	3 days	3 days	low
Full Reset	14 days	14 days	low
Cross-tolerances	cocaine, methylphenidate, pyrovalerone	cocaine, methylphenidate, pyrovalerone	low
Editorial	Locomotor sensitization in rodents (Lee 2022) is the only substance-specific tolerance-related finding. Buildup rate, half-life, full reset, and cross-tolerances are all inferred from cocaine/methylphenidate class analogy. Confidence is low due to absence of any human or animal tolerance quantification studies.
	ReasoningReasoning Locomotor sensitization in rodents (Lee 2022) is the only substance-specific tolerance-related finding. Buildup rate, half-life, full reset, and cross-tolerances are all inferred from cocaine/methylphenidate class analogy. Confidence is low due to absence of any human or animal tolerance quantification studies. Evidence basis: structural_analogy

Effects & Profile

Contraindications

Field	Published	AI Proposed	Confidence
cardiovascular Long QT syndrometrace	absolute	absolute	medium
Editorial	Rodent hERG inhibition data from Jeong 2023 is the strongest substance-specific cardiac safety signal. Absolute contraindication warranted given arrhythmia mechanism.
	ReasoningReasoning Rodent hERG inhibition data from Jeong 2023 is the strongest substance-specific cardiac safety signal. Absolute contraindication warranted given arrhythmia mechanism.
cardiovascular Concurrent QT-prolonging medicationtrace	absolute	absolute	medium
Editorial	Inferred from rodent hERG data (Jeong 2023). No prolintane-specific drug-drug QT interaction study exists, but additive hERG blockade is a well-established pharmacological principle.
	ReasoningReasoning Inferred from rodent hERG data (Jeong 2023). No prolintane-specific drug-drug QT interaction study exists, but additive hERG blockade is a well-established pharmacological principle.
pregnancy breastfeeding Pregnancytrace	absolute	absolute	low
Editorial	Single polydrug case report (Kyle 2007) plus complete absence of reproductive safety data. Absolute contraindication is precautionary given the fetal death association.
	ReasoningReasoning Single polydrug case report (Kyle 2007) plus complete absence of reproductive safety data. Absolute contraindication is precautionary given the fetal death association.
psychiatric Psychotic disorderstrace	relative	relative	medium
Editorial	Case reports document hallucinations/psychosis in overdose (Kyle 2007) and at therapeutic doses with diphenhydramine (Paya 2002). DAT inhibition → dopaminergic excess is the established class-level psychosis mechanism.
	ReasoningReasoning Case reports document hallucinations/psychosis in overdose (Kyle 2007) and at therapeutic doses with diphenhydramine (Paya 2002). DAT inhibition → dopaminergic excess is the established class-level psychosis mechanism.
other Concurrent serotonergic medicationtrace	relative	relative	medium
Editorial	Human SERT substrate activity confirmed by Kastner 2025. Serotonin syndrome risk is mechanistically supported. Tramadol interaction separately rated lethal in the database.
	ReasoningReasoning Human SERT substrate activity confirmed by Kastner 2025. Serotonin syndrome risk is mechanistically supported. Tramadol interaction separately rated lethal in the database.
neurological Seizure disorderstrace	relative	relative	low
Editorial	Class-inferred from NDRI stimulant mechanism. No prolintane-specific seizure data exist. Reference compounds: cocaine, methylphenidate.
	ReasoningReasoning Class-inferred from NDRI stimulant mechanism. No prolintane-specific seizure data exist. Reference compounds: cocaine, methylphenidate.
cardiovascular Cardiovascular diseasetrace	relative	relative	medium
Editorial	Controlled human data (Kuitunen 1984) show safety at low doses, but rodent hERG data (Jeong 2023) indicate risk at higher doses. Relative contraindication reflects this dose-dependent profile.
	ReasoningReasoning Controlled human data (Kuitunen 1984) show safety at low doses, but rodent hERG data (Jeong 2023) indicate risk at higher doses. Relative contraindication reflects this dose-dependent profile.
cardiovascular Hypertensiontrace	relative	relative	low
Editorial	Class-inferred from NDRI mechanism. Reference compounds: cocaine, methylphenidate. No prolintane-specific hypertension data.
	ReasoningReasoning Class-inferred from NDRI mechanism. Reference compounds: cocaine, methylphenidate. No prolintane-specific hypertension data.
metabolic Hyperthyroidismtrace	relative	relative	low
Editorial	Class-inferred from NDRI stimulant mechanism. No prolintane-specific data. Reference compounds: cocaine, methylphenidate, amphetamine.
	ReasoningReasoning Class-inferred from NDRI stimulant mechanism. No prolintane-specific data. Reference compounds: cocaine, methylphenidate, amphetamine.

Timeline Phases

oral

Field	Published	AI Proposed	Confidence
Onsettrace	1200–3600 sec(i=0.15)	1200–3600 sec(i=0.15)	low
Editorial	Duration phases derived from community consensus (PsychonautWiki) and cross-validated against pharmacodynamic timecourse from controlled studies: cognitive enhancement peaks at ~2.5h post-dose (Kuitunen 1984), REM suppression concentrated in first 2h of post-dose sleep (Nicholson 1980). No human pharmacokinetic data exist. Intensity weights from Phase 1 work-notes, adjusted to available phase schema.
	ReasoningReasoning Duration phases derived from community consensus (PsychonautWiki) and cross-validated against pharmacodynamic timecourse from controlled studies: cognitive enhancement peaks at ~2.5h post-dose (Kuitunen 1984), REM suppression concentrated in first 2h of post-dose sleep (Nicholson 1980). No human pharmacokinetic data exist. Intensity weights from Phase 1 work-notes, adjusted to available phase schema.
Come uptrace	1200–2700 sec(i=0.45)	1200–2700 sec(i=0.45)	low
Editorial	Duration phases derived from community consensus (PsychonautWiki) and cross-validated against pharmacodynamic timecourse from controlled studies: cognitive enhancement peaks at ~2.5h post-dose (Kuitunen 1984), REM suppression concentrated in first 2h of post-dose sleep (Nicholson 1980). No human pharmacokinetic data exist. Intensity weights from Phase 1 work-notes, adjusted to available phase schema.
	ReasoningReasoning Duration phases derived from community consensus (PsychonautWiki) and cross-validated against pharmacodynamic timecourse from controlled studies: cognitive enhancement peaks at ~2.5h post-dose (Kuitunen 1984), REM suppression concentrated in first 2h of post-dose sleep (Nicholson 1980). No human pharmacokinetic data exist. Intensity weights from Phase 1 work-notes, adjusted to available phase schema.
Peaktrace	7200–10800 sec(i=1.00)	7200–10800 sec(i=1.00)	low
Editorial	Duration phases derived from community consensus (PsychonautWiki) and cross-validated against pharmacodynamic timecourse from controlled studies: cognitive enhancement peaks at ~2.5h post-dose (Kuitunen 1984), REM suppression concentrated in first 2h of post-dose sleep (Nicholson 1980). No human pharmacokinetic data exist. Intensity weights from Phase 1 work-notes, adjusted to available phase schema.
	ReasoningReasoning Duration phases derived from community consensus (PsychonautWiki) and cross-validated against pharmacodynamic timecourse from controlled studies: cognitive enhancement peaks at ~2.5h post-dose (Kuitunen 1984), REM suppression concentrated in first 2h of post-dose sleep (Nicholson 1980). No human pharmacokinetic data exist. Intensity weights from Phase 1 work-notes, adjusted to available phase schema.
Resolutiontrace	3600–7200 sec(i=0.35)	3600–7200 sec(i=0.35)	low
Editorial	Duration phases derived from community consensus (PsychonautWiki) and cross-validated against pharmacodynamic timecourse from controlled studies: cognitive enhancement peaks at ~2.5h post-dose (Kuitunen 1984), REM suppression concentrated in first 2h of post-dose sleep (Nicholson 1980). No human pharmacokinetic data exist. Intensity weights from Phase 1 work-notes, adjusted to available phase schema.
	ReasoningReasoning Duration phases derived from community consensus (PsychonautWiki) and cross-validated against pharmacodynamic timecourse from controlled studies: cognitive enhancement peaks at ~2.5h post-dose (Kuitunen 1984), REM suppression concentrated in first 2h of post-dose sleep (Nicholson 1980). No human pharmacokinetic data exist. Intensity weights from Phase 1 work-notes, adjusted to available phase schema.
Afterglowtrace	7200–21600 sec(i=0.10)	7200–21600 sec(i=0.10)	low
Editorial	Duration phases derived from community consensus (PsychonautWiki) and cross-validated against pharmacodynamic timecourse from controlled studies: cognitive enhancement peaks at ~2.5h post-dose (Kuitunen 1984), REM suppression concentrated in first 2h of post-dose sleep (Nicholson 1980). No human pharmacokinetic data exist. Intensity weights from Phase 1 work-notes, adjusted to available phase schema.
	ReasoningReasoning Duration phases derived from community consensus (PsychonautWiki) and cross-validated against pharmacodynamic timecourse from controlled studies: cognitive enhancement peaks at ~2.5h post-dose (Kuitunen 1984), REM suppression concentrated in first 2h of post-dose sleep (Nicholson 1980). No human pharmacokinetic data exist. Intensity weights from Phase 1 work-notes, adjusted to available phase schema.

Dose Tier Summaries

thresholdtrace

low

At the threshold range, prolintane produces barely perceptible stimulation — a subtle shift toward wakefulness without clear cognitive or emotional effects. Most users report only a faint awareness that something has been ingested, without the focused sharpening that characterizes higher doses. Physical effects are negligible at this level. Cardiovascular changes are not expected. Appetite may be minimally affected. Sleep quality may be slightly altered if taken in the evening — controlled studies show REM suppression beginning at doses as low as 5 mg — but functional impairment during waking hours is unlikely at threshold doses.

Editorial

No controlled data at threshold-specific doses. Controlled sleep studies (Nicholson 1980) confirm activity at 5 mg (REM effects). Subjective threshold is community-derived. Class-inferred from cocaine/methylphenidate threshold character.

Reasoning

Evidence basis: community_consensus_large

lighttrace

medium

Light doses produce mild cognitive sharpening and increased wakefulness — a subtle but noticeable improvement in sustained attention and task focus. Mood may lift slightly, with a gentle increase in motivation enhancement. The experience remains functional and largely transparent; most users would not describe themselves as intoxicated. Physical effects are minimal. Controlled human data at 10-20 mg confirm negligible cardiovascular changes — a notable contrast to sympathomimetic stimulants at equivalent doses. Appetite suppression is mild. REM sleep is reduced if prolintane is taken before sleep at 5-10 mg, though sleep latency and slow-wave sleep are preserved. Users taking light doses in the afternoon may notice slightly disrupted dream recall without overt insomnia.

Editorial

Controlled human data (Kuitunen 1984) at 10-20 mg confirm cognitive enhancement with minimal CV effects. Sleep studies (Nicholson 1980) at 5-10 mg confirm REM suppression. This tier has the strongest evidence base of any prolintane dose range.

Reasoning

Evidence basis: community_consensus_large

commontrace

medium

Common doses produce clear stimulation with noticeable focus enhancement, thought acceleration, and wakefulness. Cognitive throughput improves measurably — controlled studies confirm significant performance gains on cognitive tasks at the lower end of this range. Mood elevation becomes apparent, though cognitive euphoria remains moderate rather than intense. The compulsive redosing urge may emerge at this level. Physically, appetite suppression becomes pronounced. Stimulation is clear but typically smooth rather than jittery. Dose-dependent REM suppression intensifies — at 15-30 mg, both delayed REM onset and reduced total REM sleep are documented, with increased awakenings during early-night sleep. Functional impairment is minimal during the active period, but insomnia is likely if taken within 6 hours of intended sleep. The 4-6 hour total duration is manageable for daytime use.

Editorial

Controlled human studies span this range: Kuitunen 1984 (10-20 mg cognitive performance), Nicholson 1980 (15-30 mg sleep disruption). Community dose ranges from PsychonautWiki. Compulsive redosing inferred from rodent self-administration data (Lee 2022).

Reasoning

Evidence basis: community_consensus_large

strongtrace

low

Strong doses produce pronounced stimulation with significant thought acceleration, heightened restlessness, and potential anxiety. Focus may begin to narrow excessively rather than enhance broadly. The compulsive redosing urge intensifies, and ego inflation may become apparent. Irritability and muscle tension can emerge. Cardiovascular effects may become clinically relevant at this level — while therapeutic doses show minimal cardiac changes, the hERG channel inhibition documented in rodent models suggests dose-dependent arrhythmia risk. Appetite suppression is strong and sustained. Insomnia is probable for 6-8 hours after dosing. Prolonged wakefulness at this dose level may precipitate anxiety or paranoia, particularly in predisposed individuals. The functional quality of the experience begins to deteriorate relative to common doses.

Editorial

No controlled human data exist at strong doses (45-60 mg). Cardiovascular risk inferred from rodent hERG data (Jeong 2023). Psychological effects inferred from NDRI class and dose-response extrapolation. Community-derived dose range from PsychonautWiki.

Reasoning

Evidence basis: community_consensus_large

heavytrace

low

Heavy doses carry significant risk of adverse psychological and cardiovascular effects. Thought disorganization, delusions, and hallucinations are documented in overdose settings — though published cases involved polydrug use, preventing isolation of prolintane's contribution. Psychosis is listed among overdose-associated outcomes. Paranoia and pronounced agitation may develop. hERG-related cardiac risk becomes clinically significant at supratherapeutic concentrations, with QT prolongation and ventricular arrhythmia risk documented in rodent models. Confusion and inability to follow commands were observed in a clinical case involving prolintane at undefined doses with concurrent medications. Katovit tablets contained 200 mg per tablet — far above this threshold — suggesting that chronic users may have developed substantial tolerance. Users without tolerance should treat doses above 60 mg as carrying disproportionate risk relative to any additional stimulant effect.

Editorial

No controlled data at heavy doses. Overdose case reports (Kyle 2007) document confusion, agitation, hallucinations, psychosis, and death — all in polydrug context. hERG/QT data from rodent models (Jeong 2023). Katovit 200 mg tablet context from Gaulier 2002. Community-derived threshold from PsychonautWiki.

Reasoning

Evidence basis: community_consensus_large

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

6 strong · 9 moderate · 11 weak

[1]
strong
Prolintane analogs as hybrid monoamine transporter ligands: Structural determinants and species differences.
Kastner N, Islam MN, Dybek M, Roth E, Heisinger S, Holy M, Jäntsch K, Walther D, Stockner T, Baumann MH, Brandt SD, Wallach J, Sitte HH, Kudlacek O · 2025 · The Journal of Biological Chemistry
doi.org/10.1016/j.jbc.2025.110903 pubmed 4119771616 claims checked12 verified4 partial
[2]
moderate
The Psychonauts' World of Cognitive Enhancers
Napoletano F, Schifano F, Corkery JM, Guirguis A, Arillotta D, Zangani C, Vento A · 2020 · Frontiers in Psychiatry
doi.org/10.3389/fpsyt.2020.546796 pubmed 330244361 claim checked1 verified
[3]
weak
S6. Stimulants - WADA Anti-Doping Prohibited List
World Anti-Doping Agency · 2025
linkno claims checked
[4]
moderate
The abuse potential of prolintane in rodents: Behavioral pharmacology approaches.
Lee W, Lee JW, Kim JM, Hong YK, Kim MS, Choi SO, Kang MS · 2022 · Neuropharmacology
doi.org/10.1016/j.neuropharm.2021.108917 pubmed 3489611712 claims checked8 verified2 partial1 inconclusive1 not supported
[5]
weak
Domestic abuse of the European rave drug prolintane.
Kyle PB, Daley WP · 2007 · Journal of Analytical Toxicology
pubmed 1772589011 claims checked5 verified1 inconclusive5 not supported
[6]
moderate
Neurotoxic and cardiotoxic effects of N-methyl-1-(naphthalen-2-yl)propan-2-amine (methamnetamine) and 1-phenyl-2-pyrrolidinylpentane (prolintane).
Jeong S, Yoon KS, Lee JM, Jo ES, Kim D, Choi SO · 2023 · Drug and Chemical Toxicology
doi.org/10.1080/01480545.2022.2049289 pubmed 352962058 claims checked8 verified
[7]
moderate
Effects of prolintane on 3,4-dihydroxyphenylacetic acid concentration in rat brain after spiperone treatment.
Fuller RW, Snoddy HD · 1979 · Pharmacology, Biochemistry and Behavior
pubmed 5725524 claims checked4 verified
[8]
strong
Comparison of the acute physical and mental effects of ephedrine, fenfluramine, phentermine and prolintane.
Kuitunen T, Kärkkäinen S, Ylitalo P · 1984 · Methods and Findings in Experimental and Clinical Pharmacology
pubmed 64719708 claims checked6 verified2 partial
[9]
strong
Wakefulness and reduced rapid eye movement sleep: studies with prolintane and pemoline.
Nicholson AN, Stone BM, Jones MM · 1980 · British Journal of Clinical Pharmacology
pubmed 74372584 claims checked2 verified2 partial
[10]
weak
Prolintane synthesis history and patent data
Various web sources (grokipedia, benchchem) · 2024
linkno claims checked
[11]
weak
Prolintane - Wikipedia
Wikipedia contributors · 2024
linkno claims checked
[12]
weak
[New drugs at 'rave parties': ketamine and prolintane].
Gaulier JM, Canal M, Pradeille JL, Marquet P, Lachâtre G · 2002 · Acta Clinica Belgica
pubmed 119744432 claims checked1 verified1 partial
[13]
weak
Prolintane: a 'masked' amphetamine.
Martínez-Mir I, Catalán C, Palop V · 1997 · The Annals of Pharmacotherapy
pubmed 9034438no claims checked
[14]
strong
Pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA).
Docherty JR · 2008 · British Journal of Pharmacology
doi.org/10.1038/bjp.2008.124 pubmed 18500382no claims checked
[15]
strong
[Combination of phenylpyrrolidinopentane (Katovit) and oxazepam (Adumbran). A double-blind comparison with opipramol (Insidon) in depressive syndromes].
Gmür M, Angst J · 1977 · International Pharmacopsychiatry
pubmed 3304392 claims checked2 verified
[16]
moderate
The psychoactive cathinone derivative pyrovalerone alters locomotor activity and decreases dopamine receptor expression in zebrafish (Danio rerio).
Souders CL, Davis RH, Qing H, Liang X, Febo M, Martyniuk CJ · 2019 · Brain and Behavior
doi.org/10.1002/brb3.1420 pubmed 316256914 claims checked2 verified1 partial1 inconclusive
[17]
weak
PROLINTANE - NCATS Inxight Drugs
National Center for Advancing Translational Sciences · 2024
linkno claims checked
[18]
moderate
The biotransformation of nitrogen containing xenobiotics to lactams.
Vickers S, Polsky SL · 2000 · Current Drug Metabolism
pubmed 114650444 claims checked4 verified
[19]
weak
Prolintane - PsychonautWiki
PsychonautWiki contributors · 2024
linkno claims checked
[20]
strong
Heterocyclic amphetamine derivatives and caffeine on sleep in man.
Nicholson AN, Stone BM · 1980 · British Journal of Clinical Pharmacology
pubmed 61019603 claims checked1 verified2 partial
[21]
weak
Visual hallucinations induced by the combination of prolintane and diphenhydramine.
Payá B, Guisado JA, Vaz FJ, Crespo-Facorro B · 2002 · Pharmacopsychiatry
pubmed 118191555 claims checked4 verified1 partial
[22]
moderate
Metabolism of prolintane in rats and the effect of prolintane metabolites on general activities in mice.
Yoshihara S, Yoshimura H · 1974 · Xenobiotica
pubmed 41545402 claims checked1 verified1 inconclusive
[23]
moderate
The Pharmacological Profile of Second Generation Pyrovalerone Cathinones and Related Cathinone Derivative.
Kolaczynska KE, Thomann J, Hoener MC, Liechti ME · 2021 · International journal of molecular sciences
doi.org/10.3390/ijms22158277 pubmed 343610401 claim checked1 verified
[24]
weak
Lethal combination of tramadol and multiple drugs affecting serotonin
Ripple MG, Pestaner JP, Levine BS, Smialek JE · 2000 · American Journal of Forensic Medicine and Pathology
pubmed 111118001 claim checked1 verified
[25]
weak
Serotonin Toxicity Precipitated by Tramadol in the Setting of Polypharmacy: A Case of Serotonin Syndrome.
Ruiz de Villa A, Jones T, Lleshi A, Macahuachi M, Lamar K, Bazikian Y · 2021 · Cureus
doi.org/10.7759/cureus.20059 pubmed 349879321 claim checked1 not supported
[26]
moderate
Human pharmacology of MDMA: pharmacokinetics, metabolism, and disposition
de la Torre R, Farré M, Roset PN, Pizarro N, Abanades S, Segura M, Segura J, Camí J · 2004 · Therapeutic Drug Monitoring
pubmed 152281541 claim checked1 verified

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.

summary10 claims4verified6partial

verifiedProlintane (1-(1-phenylpentan-2-yl)pyrrolidine) is a synthetic pyrrolidine-class stimulant that acts primarily as a norepinephrine-dopamine reuptake inhibitor (NDRI), with recently characterized serotonin-releasing activity at the human serotonin transporter (hSERT)^[1]97%

Verified

Abstract directly confirms DAT/NET reuptake inhibition and hSERT-mediated ionic currents and serotonin efflux, classifying prolintane as a hybrid compound at human monoamine transporters.

Prolintane is a synthetic stimulant that acts by inhibiting the uptake of dopamine and norepinephrine into neurons... Prolintane and analogs induced hSERT-mediated ionic currents and serotonin efflux — classifying them as hybrid compounds at human monoamine transporters.

checked by claude-sonnet-4-6 · May 13, 2026

partialProlintane was synthesized in the 1950s by Thomae (a Boehringer Ingelheim predecessor) and prescribed across Europe, South Africa, and Australia for fatigue, narcolepsy, and ADHD before market withdrawal in 2001 due to abuse liability concerns^[1]90%

Partial

Abstract confirms therapeutic use for ADHD and narcolepsy and discontinuation due to abuse liability, but does not mention the 1950s synthesis date, Thomae/Boehringer Ingelheim, specific geographic markets (Europe/South Africa/Australia), fatigue as an indication, or the 2001 withdrawal year.

Initially prescribed for attention deficit hyperactivity disorder and narcolepsy, its medical use was discontinued due to concerns about abuse liability.

checked by claude-sonnet-4-6 · May 13, 2026

partialThe compound's research significance has grown since 2022, when rodent behavioral pharmacology studies confirmed its rewarding properties via conditioned place preference and intravenous self-administration paradigms, and a 2025 study revealed a species-dependent serotonergic mechanism absent in earlier rat-based assays.^[4]85%

Partial

Abstract (citation [2]) supports the 2022 rodent CPP and IV self-administration findings, but contains no information about the 2025 species-dependent serotonergic mechanism, which would be from citation [1].

Prolintane increased locomotor activity, produced conditioned place preference, supported intravenous self-administration.

checked by claude-sonnet-4-6 · May 13, 2026

Partial

Abstract (citation [1]) supports the 2025 species-dependent serotonergic mechanism (hSERT efflux, species differences), but contains no information about the 2022 rodent CPP/self-administration behavioral pharmacology findings.

Prolintane and analogs induced hSERT-mediated ionic currents and serotonin efflux — classifying them as hybrid compounds at human monoamine transporters.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedProlintane blocks the dopamine transporter (DAT) and norepinephrine transporter (NET) in a manner pharmacologically analogous to cocaine and methylphenidate rather than amphetamine — that is, it inhibits reuptake without inducing vesicular release^[7]97%

Verified

Abstract directly confirms prolintane acts as a reuptake inhibitor rather than a releaser, with mechanism more similar to methylphenidate, cocaine, and amfonelic acid than amphetamine.

Compared to amphetamine, prolintane mechanism more similar to methylphenidate, cocaine, amfonelic acid — acting as a reuptake inhibitor rather than releaser.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedAt human transporters, however, prolintane also functions as a SERT substrate, inducing serotonin efflux — a hybrid mechanism not observed in rat tissue^[1]93%

Verified

Abstract confirms hSERT-mediated ionic currents and serotonin efflux at human transporters, with the paper's scope explicitly covering species differences (hSERT vs rSERT) consistent with the rat tissue claim.

Prolintane and analogs induced hSERT-mediated ionic currents and serotonin efflux — classifying them as hybrid compounds at human monoamine transporters. SERT inhibitory potencies at least 10-fold weaker at hSERT vs rSERT.

checked by claude-sonnet-4-6 · May 13, 2026

partialThe subjective profile at therapeutic doses (10–20 mg oral) is characterized by mild cognitive enhancement, wakefulness promotion, and dose-dependent REM sleep suppression, with set, setting, and individual catecholamine tone modulating the experience.^[8]80%

Partial

Abstract (citation [7]) confirms cognitive enhancement at 10–20 mg oral, but contains no data on wakefulness promotion or REM sleep suppression, which are from different citations.

Prolintane at 2.5h improved sign recording test performance (mental task). Doses in 10-20mg range commonly used medically.

checked by claude-sonnet-4-6 · May 13, 2026

Partial

Abstract (citation [8]) confirms REM suppression and wakefulness effects but at 15–30 mg doses, not the 10–20 mg claimed. No cognitive enhancement data present.

Prolintane 15 and 30mg reduced REM sleep (delayed first REM period, reduced total REM) in 6 healthy males. Increased awakenings early in the night at higher doses.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedCardiovascular safety data are limited to rodent models, where prolintane produces hERG potassium channel inhibition and QT interval prolongation — markers of ventricular arrhythmia risk^[6]97%

Verified

Abstract directly confirms hERG potassium channel inhibition and QT prolongation in rodents as markers of ventricular arrhythmia risk.

QT prolongation and hERG potassium channel inhibition observed at certain concentrations — ventricular arrhythmia risk.

checked by claude-sonnet-4-6 · May 13, 2026

partialRodent studies confirm abuse potential via mesolimbic dopamine elevation and self-administration, though at a moderate level relative to methamphetamine^[4]80%

Partial

Abstract confirms mesolimbic dopamine elevation and self-administration at moderate abuse potential level, but the comparison is to cocaine (not methamphetamine as the claim states).

Results indicate moderate abuse potential similar to cocaine at moderate level.

checked by claude-sonnet-4-6 · May 13, 2026

history7 claims5verified1partial1inconclusive

partialThe Spanish pharmaceutical company FHER marketed the compound as Katovit — orange-coated tablets containing 200 mg prolintane combined with vitamins, sold over the counter at approximately €1.93 per 20-tablet pack^[12]82%

Partial

Abstract confirms orange tablets branded Katovit, 200 mg prolintane, vitamins, OTC in Spain, at low price. However, manufacturer FHER and the specific price of €1.93 per 20-tablet pack are not mentioned.

Prolintane found in orange tablets ('Katovit') sold at rave parties in south-west France. Katovit: available in Spain OTC with vitamins, 200mg prolintane per tablet, sold at low price.

checked by claude-sonnet-4-6 · May 13, 2026

inconclusiveClinical indications during its period of active medical use included ADHD, narcolepsy, fatigue and asthenia, orthostatic hypotension, and depressive syndromes^[5]65%

Inconclusive

Abstract focuses on two US abuse cases and notes historical prescribing in Africa, Australia, and Europe, but does not enumerate clinical indications. The specific indications (fatigue, asthenia, orthostatic hypotension, depressive syndromes) are likely in the paper body but absent from the abstract.

Notes prolintane not detected on routine urine drug screen.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedA double-blind trial by Gmür and Angst (1977) evaluated prolintane (as Katovit) in combination with oxazepam against opipramol for depressive syndromes^[15]93%

Verified

PubMed record description confirms a double-blind study of prolintane (Katovit brand) combined with oxazepam for depressive syndromes compared with opipramol.

No abstract available in PubMed record. Double-blind study of prolintane (Katovit brand) combined with oxazepam for depressive syndromes, compared with opipramol.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedMedical use was discontinued more broadly as abuse liability became increasingly recognized.^[1]97%

Verified

Abstract directly confirms medical use was discontinued due to concerns about abuse liability.

its medical use was discontinued due to concerns about abuse liability.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedGaulier et al. (2002) documented prolintane use at rave parties in southwest France, where Katovit tablets circulated as a cheap stimulant^[12]97%

Verified

Abstract directly confirms Katovit found at rave parties in south-west France, sold at low price.

Prolintane found in orange tablets ('Katovit') sold at rave parties in south-west France... sold at low price.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedThe first medically documented cases of prolintane abuse in the United States were reported by Kyle and Daley in 2007^[5]95%

Verified

Abstract explicitly states these were the first US-documented cases of prolintane abuse. Author and year are citation metadata.

First US-documented cases of prolintane abuse.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedSince the mid-2010s, prolintane has appeared on research chemical markets as a novel psychoactive substance (NPS).^[2]88%

Verified

Abstract confirms prolintane is listed among substances found on psychonaut forums and research chemical markets, consistent with NPS classification.

Review of NPS cognitive enhancers. Prolintane listed among substances found on psychonaut forums and research chemical markets.

checked by claude-sonnet-4-6 · May 13, 2026

chemistry2 claims2verified

verifiedThe compound is structurally related to pyrovalerone, which is its beta-keto (carbonyl-bearing) derivative^[16]97%

Verified

Abstract directly confirms pyrovalerone is '4-methyl-β-keto-prolintane', establishing it as the beta-keto derivative of prolintane.

Pyrovalerone (4-methyl-β-keto-prolintane) is a synthetic cathinone.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedThe absence of a carbonyl group at the benzylic position distinguishes prolintane from its beta-keto analog pyrovalerone.^[16]90%

Verified

The beta-keto designation in '4-methyl-β-keto-prolintane' confirms that the carbonyl group is a feature of pyrovalerone absent in prolintane. The claim identifies one key structural distinction.

Pyrovalerone (4-methyl-β-keto-prolintane) is a synthetic cathinone.

checked by claude-sonnet-4-6 · May 13, 2026

pharmacology11 claims8verified2partial1inconclusive

partialThese values are consistent with the pharmacodynamic timecourse observed in controlled sleep and performance studies (cognitive enhancement at 2.5 hours post-dose; REM suppression concentrated in the first 2 hours of post-dose sleep), but formal PK confirmation is lacking.^[8]78%

Partial

Abstract (citation [7]) confirms cognitive enhancement at 2.5 h post-dose. No REM suppression data is present in this abstract — that data comes from citations [8] and [9].

Prolintane at 2.5h improved sign recording test performance (mental task).

checked by claude-sonnet-4-6 · May 13, 2026

verifiedThis mechanism is pharmacologically analogous to cocaine and methylphenidate — not amphetamine — in that prolintane inhibits transporter-mediated reuptake without inducing vesicular monoamine release.^[1]88%

Verified

Abstract confirms DAT/NET reuptake inhibition mechanism, consistent with cocaine/methylphenidate class. The explicit amphetamine comparison is not stated but the reuptake inhibitor mechanism (not release) is confirmed.

Prolintane is a synthetic stimulant that acts by inhibiting the uptake of dopamine and norepinephrine into neurons.

checked by claude-sonnet-4-6 · May 13, 2026

Verified

Abstract directly and explicitly confirms the cocaine/methylphenidate analogy (reuptake inhibitor) vs amphetamine (releaser) distinction.

Compared to amphetamine, prolintane mechanism more similar to methylphenidate, cocaine, amfonelic acid — acting as a reuptake inhibitor rather than releaser.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedFuller and Snoddy (1979) established this distinction by demonstrating that prolintane markedly enhanced 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations in rat brain following spiperone treatment — a neurochemical pattern characteristic of DAT inhibitors rather than DAT releasers^[7]95%

Verified

Abstract directly confirms enhanced DOPAC in spiperone-treated rats and the reuptake inhibitor characterization. Author names/date are inherent citation metadata.

Prolintane enhanced increase in DOPAC (dopamine metabolite) in rats treated with spiperone. Compared to amphetamine, prolintane mechanism more similar to methylphenidate, cocaine, amfonelic acid — acting as a reuptake inhibitor rather than releaser.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedKastner et al., using radiotracer flux assays in HEK293 cells expressing human transporters and parallel experiments in rat brain synaptosomes, demonstrated that prolintane is a hybrid compound — a potent DAT and NET inhibitor that also acts as a SERT substrate, inducing hSERT-mediated ionic currents and tritiated serotonin efflux at the human serotonin transporter^[1]93%

Verified

Abstract confirms hybrid classification, DAT/NET inhibition, and hSERT-mediated ionic currents and serotonin efflux. Methodological details (HEK293 cells, radiotracer, synaptosomes) are in the full text but the core findings are confirmed.

Prolintane and analogs induced hSERT-mediated ionic currents and serotonin efflux — classifying them as hybrid compounds at human monoamine transporters.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedThis serotonin-releasing activity was not observed in rat brain synaptosomes, representing a significant species difference that means prior rat-only pharmacology underestimated prolintane's serotonergic activity in humans.^[1]90%

Verified

Abstract highlights species differences (hSERT vs rSERT) and restricts the hybrid/serotonin efflux characterization to human monoamine transporters, supporting inference that rat-based assays missed this activity.

SERT inhibitory potencies at least 10-fold weaker at hSERT vs rSERT... classifying them as hybrid compounds at human monoamine transporters.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedAn earlier case report by Paya et al. (2002) described prolintane as a dopamine releaser and diphenhydramine as a dopamine reuptake inhibitor — characterizations that reverse the established pharmacology^[21]95%

Verified

Abstract confirms the case report proposed prolintane as dopamine releaser and diphenhydramine as reuptake inhibitor — exactly as the claim states.

Proposed mechanism: prolintane induces dopamine release at synapse; diphenhydramine inhibits dopamine reuptake — synergistic dopaminergic potentiation.

checked by claude-sonnet-4-6 · May 13, 2026

inconclusiveYoshihara and Yoshimura (1974) conducted the foundational metabolism study in rats, identifying prolintane metabolites and assessing their pharmacological activity in mice^[22]70%

Inconclusive

No abstract available in PubMed record. The PubMed record description confirms rats/mice study design but is insufficient for claim verification per protocol.

No abstract available in PubMed record. Study of prolintane metabolites in rats and their pharmacological activity in mice.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedVickers and Polsky (2000) described the general biotransformation pathway for pyrrolidine-containing xenobiotics, including prolintane, to lactam metabolites^[18]97%

Verified

Abstract directly confirms this review covers lactam metabolite formation from N-heterocyclic compounds including prolintane via iminium ion pathway.

Review of lactam metabolite formation from N-heterocyclic compounds including prolintane. Pathway involves iminium ion intermediates oxidized by aldehyde oxidases, or via CYP450 through carbinolamine.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedSpecies differences in lactam formation rates arise from variation in aldehyde oxidase and CYP450 isozyme expression and concentration^[18]95%

Verified

Abstract directly confirms species differences in lactam formation based on aldehyde oxidase and CYP450 activity.

Identifies species differences in lactam formation based on aldehyde oxidase and CYP450 activity.

checked by claude-sonnet-4-6 · May 13, 2026

Partial

Abstract (citation [9]) confirms REM suppression concentrated in the first 2 h after sleep onset. No cognitive enhancement data is present in this abstract.

prolintane HCl 5 and 10mg reduced REM sleep in first 2h after sleep onset; no change in sleep latencies or slow wave sleep.

checked by claude-sonnet-4-6 · May 13, 2026

neuroscience7 claims6verified1inconclusive

verifiedMesolimbic reward pathway: Lee et al. (2022) demonstrated that a single intraperitoneal injection of prolintane at 20 mg/kg significantly increased extracellular dopamine concentrations in the striatum via in vivo microdialysis^[4]97%

Verified

Abstract directly confirms: single injection, 20 mg/kg IP, significantly increased extracellular dopamine in striatum.

Single injection (20 mg/kg IP) significantly increased extracellular dopamine in striatum.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedThis mesolimbic dopamine elevation is the canonical neural substrate of stimulant reward and explains the conditioned place preference and intravenous self-administration observed in the same study^[4]90%

Verified

Abstract confirms all three observations (striatal dopamine elevation, CPP, IV self-administration) in the same study. The causal interpretation is standard neuroscience.

Prolintane increased locomotor activity, produced conditioned place preference, supported intravenous self-administration... Single injection (20 mg/kg IP) significantly increased extracellular dopamine in striatum.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedPrefrontal executive modulation: The cognitive enhancement observed in human studies — improved sign recording performance at 2.5 hours post-dose — is consistent with catecholamine-mediated potentiation of prefrontal cortical function^[8]88%

Verified

Abstract confirms improved sign recording performance at 2.5 h post-dose. PFC catecholamine interpretation is standard pharmacological inference for a catecholaminergic reuptake inhibitor improving cognition.

Prolintane at 2.5h improved sign recording test performance (mental task).

checked by claude-sonnet-4-6 · May 13, 2026

verifiedSerotonergic modulation: The species-dependent SERT substrate activity identified by Kastner et al. (2025) — present at human but not rat transporters — implies that prolintane induces serotonin efflux in human brain in addition to catecholamine reuptake inhibition^[1]92%

Verified

Abstract confirms hSERT-mediated serotonin efflux at human transporters with species differences noted, supporting the inference of human brain serotonin efflux.

Prolintane and analogs induced hSERT-mediated ionic currents and serotonin efflux — classifying them as hybrid compounds at human monoamine transporters. SERT inhibitory potencies at least 10-fold weaker at hSERT vs rSERT.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedNeuroinflammatory signals: Jeong et al. (2023) documented shortened IBA-1 (ionized calcium-binding adaptor molecule 1) immunoreactive process length in rodent brain tissue following prolintane administration^[6]97%

Verified

Abstract directly confirms shortened IBA-1 microglial marker length suggesting neuroinflammation.

IHC showed shortened IBA-1 (microglial marker) length suggesting neuroinflammation.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedDAT blockade increases dopamine in the nucleus accumbens, potentiating the wanting signal — the motivational drive to seek the drug — while the subjective liking component appears moderate based on the partial cocaine substitution (38.57% cocaine-appropriate responding)^[4]88%

Verified

Abstract confirms striatal (includes nucleus accumbens) dopamine elevation and 38.57% cocaine-appropriate responding. The wanting/liking framework is standard neuroscience applied to these data.

Single injection (20 mg/kg IP) significantly increased extracellular dopamine in striatum... partially substituted for cocaine in drug discrimination (38.57% at up to 10 mg/kg).

checked by claude-sonnet-4-6 · May 13, 2026

inconclusiveSensitization model: Locomotor sensitization to prolintane in rodents suggests progressive enhancement of mesolimbic dopamine responses with repeated exposure — a neuroadaptation associated with increasing motivation to use and escalating patterns of consumption in the stimulant class.^[4]65%

Inconclusive

Abstract confirms acute locomotor stimulation but does not mention sensitization (which requires repeated dosing paradigms). The sensitization claim may be in the full paper but is not supported by the abstract.

Prolintane increased locomotor activity.

checked by claude-sonnet-4-6 · May 13, 2026

receptor pharmacology4 claims2verified1partial1inconclusive

verifiedThe Kastner et al. (2025) study reports assay data for prolintane and novel analogs but presents results primarily as IC₅₀ ratios and relative potency comparisons rather than isolated prolintane values in the abstract^[1]90%

Verified

Abstract uses relative comparisons ('at least 10-fold weaker', 'potent uptake inhibition', 'weaker effects') rather than providing absolute IC₅₀ values for prolintane, consistent with the claim.

SERT inhibitory potencies at least 10-fold weaker at hSERT vs rSERT.

checked by claude-sonnet-4-6 · May 13, 2026

partialSERT: ≥10-fold weaker than DAT at human transporters; substrate activity (serotonin efflux) at hSERT; no substrate activity in rat synaptosomes^[1]80%

Partial

Abstract confirms SERT activity is weaker than DAT/NET, and hSERT substrate activity (serotonin efflux) exists. However, the '≥10-fold' figure in the abstract refers to hSERT vs rSERT (species comparison), not SERT vs DAT potency as the claim states. The 'no rat synaptosome substrate activity' is implied but not explicit.

SERT inhibitory potencies at least 10-fold weaker at hSERT vs rSERT... Prolintane and analogs induced hSERT-mediated ionic currents and serotonin efflux.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedAcross the pyrovalerone-type class, DAT IC₅₀ values ranged from 0.02 to 8.7 µM, NET IC₅₀ values from 0.03 to 4.6 µM, and SERT activity was absent below 10 µM in rat tissue preparations^[23]98%

Verified

Abstract directly confirms: DAT IC50 = 0.02–8.7 µM, NET IC50 = 0.03–4.6 µM, no SERT activity < 10 µM.

All are potent DAT (IC50=0.02-8.7μM) and NET (IC50=0.03-4.6μM) inhibitors with no SERT activity <10μM.

checked by claude-sonnet-4-6 · May 13, 2026

inconclusivePyrovalerone itself — the beta-keto derivative of prolintane — falls within this range^[16]65%

Inconclusive

Abstract confirms pyrovalerone inhibits DAT and NET, but provides no IC₅₀ values to verify it falls within the 0.02–8.7 µM DAT / 0.03–4.6 µM NET ranges. Quantitative data would be in the full paper.

Pyrovalerone (4-methyl-β-keto-prolintane) is a synthetic cathinone. Inhibits DAT and NET.

checked by claude-sonnet-4-6 · May 13, 2026

pharmacokinetic detail6 claims4verified2partial

verifiedCognitive performance enhancement peaks at approximately 2.5 hours after oral administration of 10–20 mg^[8]97%

Verified

Abstract directly confirms improved performance at 2.5 h with 10–20 mg oral doses.

Prolintane at 2.5h improved sign recording test performance (mental task). Doses in 10-20mg range commonly used medically.

checked by claude-sonnet-4-6 · May 13, 2026

partialREM sleep suppression is concentrated in the first 2 hours after sleep onset when prolintane is administered before sleep at doses of 5–30 mg^[20]82%

Partial

Abstract (citation [9]) confirms first-2-h REM suppression at 5–10 mg. The claim states 5–30 mg but this abstract only covers 5–10 mg; the 15–30 mg data is from citation [8].

prolintane HCl 5 and 10mg reduced REM sleep in first 2h after sleep onset.

checked by claude-sonnet-4-6 · May 13, 2026

partialREM sleep suppression is concentrated in the first 2 hours after sleep onset when prolintane is administered before sleep at doses of 5–30 mg^[9]78%

Partial

Abstract (citation [8]) confirms REM suppression at 15–30 mg but does not specify suppression is 'concentrated in the first 2 hours' — that timing detail appears in citation [9].

Prolintane 15 and 30mg reduced REM sleep (delayed first REM period, reduced total REM) in 6 healthy males.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedThe metabolic fate of prolintane follows the general pyrrolidine biotransformation pathway described by Vickers and Polsky (2000)^[18]95%

Verified

Abstract confirms this review covers prolintane's pyrrolidine (N-heterocyclic) biotransformation to lactam via iminium ion, CYP450, and aldehyde oxidase pathways.

Review of lactam metabolite formation from N-heterocyclic compounds including prolintane. Pathway involves iminium ion intermediates oxidized by aldehyde oxidases, or via CYP450 through carbinolamine.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedSpecies differences in the relative contribution of CYP450 versus aldehyde oxidase to this final step produce variable lactam formation rates across species.^[18]95%

Verified

Abstract directly confirms species differences in lactam formation based on aldehyde oxidase and CYP450 activity.

Identifies species differences in lactam formation based on aldehyde oxidase and CYP450 activity.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedYoshihara and Yoshimura (1974) conducted the only published metabolic study, administering prolintane to rats and evaluating the pharmacological activity of the resulting metabolites in mice^[22]80%

Verified

PubMed record description confirms the study administered prolintane to rats and evaluated metabolite pharmacological activity in mice. 'Only published' is uncontradicted by the abstract.

No abstract available in PubMed record. Study of prolintane metabolites in rats and their pharmacological activity in mice.

checked by claude-sonnet-4-6 · May 13, 2026

effects overview1 claim1verified

verifiedAmong NDRI stimulants, prolintane sits between methylphenidate and cocaine in reinforcing efficacy — producing conditioned place preference and self-administration in rodents, but with only partial substitution for cocaine in discrimination paradigms (38.57% cocaine-appropriate responding)^[4]90%

Verified

Abstract confirms CPP, IV self-administration, and 38.57% partial cocaine substitution — the empirical basis for prolintane's intermediate reinforcing efficacy position.

produced conditioned place preference, supported intravenous self-administration, and partially substituted for cocaine in drug discrimination (38.57% at up to 10 mg/kg).

checked by claude-sonnet-4-6 · May 13, 2026

safety29 claims22verified1partial6not supported

not supportedHallucinations and psychosis are documented overdose outcomes, and hallucinations occurred at therapeutic doses in combination with diphenhydramine.^[5]85%

Not supported

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

Abstract (citation [4]) documents confusion/agitation and fetal death in polysubstance cases. Neither hallucinations nor psychosis are documented as overdose outcomes in this paper. The diphenhydramine combination hallucination is from a different source (citation [6]).

Case 1: 34yo male, confused and agitated... Case 2: 26yo female, intrauterine fetal death.

checked by claude-sonnet-4-6 · May 13, 2026

not supportedOverdoses of prolintane may produce hallucinations, psychosis, and death^[5]85%

Not supported

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

Abstract documents confusion and agitation (Case 1) and intrauterine fetal death (Case 2) in polysubstance settings. Hallucinations are not mentioned, psychosis is not documented, and no adult death attributable to prolintane is described. The fetal death is in a polysubstance context.

Case 1: 34yo male, confused and agitated... Case 2: 26yo female, intrauterine fetal death, positive for prolintane plus cannabinoids, cocaine, nicotine, hydrocodone.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedBoth documented clinical cases involved polysubstance use — a 34-year-old male with confusion, agitation, and inability to follow commands (concurrent amitriptyline, nortriptyline, nicotine) and a 26-year-old female with intrauterine fetal death (concurrent cannabinoids, cocaine, nicotine, hydrocodone) — preventing isolation of prolintane's individual toxicological contribution.^[5]98%

Verified

Abstract exactly describes both cases with the correct ages, clinical presentations, and polysubstance profiles.

Case 1: 34yo male, confused and agitated, GC-MS positive for prolintane, amitriptyline, nortriptyline, nicotine. Case 2: 26yo female, intrauterine fetal death, positive for prolintane plus cannabinoids, cocaine, nicotine, hydrocodone.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedJeong et al. (2023) evaluated prolintane's cardiac safety in mice and rats and documented hERG potassium channel inhibition — the canonical biomarker for drug-induced QT interval prolongation and ventricular arrhythmia risk^[6]97%

Verified

Abstract directly confirms hERG potassium channel inhibition and QT prolongation with ventricular arrhythmia risk in rodents.

QT prolongation and hERG potassium channel inhibition observed at certain concentrations — ventricular arrhythmia risk.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedThe authors concluded that prolintane "cannot be excluded" from causing ventricular arrhythmia risk.^[6]88%

Verified

Abstract confirms ventricular arrhythmia risk was identified, and notes prolintane is 'not directly myocardiotoxic' — a qualified finding consistent with a 'cannot be excluded' conclusion.

QT prolongation and hERG potassium channel inhibition observed at certain concentrations — ventricular arrhythmia risk. Not directly myocardiotoxic.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedAt therapeutic oral doses (10–20 mg), prolintane produced minimal cardiovascular changes in a controlled human comparison study, in contrast to ephedrine^[8]98%

Verified

Abstract directly confirms minimal cardiovascular effects at 10–20 mg vs ephedrine which significantly raised BP and HR.

Minimal cardiovascular effects (vs ephedrine which significantly raised BP and HR). Doses in 10-20mg range commonly used medically.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedJeong et al. (2023) documented shortened IBA-1 immunoreactive process length in rodent brain following prolintane administration — a marker of microglial activation and neuroinflammation that may disrupt synaptic contacts^[6]97%

Verified

Abstract directly confirms shortened IBA-1 (microglial marker) length suggesting neuroinflammation.

IHC showed shortened IBA-1 (microglial marker) length suggesting neuroinflammation.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedReduced motor coordination was observed in both mice and rats^[6]90%

Verified

Abstract confirms reduced motor coordination in rodents (encompasses mice and rats). The title indicates the study used multiple rodent species.

Prolintane reduced motor coordination in rodents.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedProlintane was detected in a case involving intrauterine fetal death, though polysubstance use (cannabinoids, cocaine, nicotine, hydrocodone) prevents causal attribution^[5]98%

Verified

Abstract directly confirms Case 2: intrauterine fetal death with prolintane plus listed polysubstance profile.

Case 2: 26yo female, intrauterine fetal death, positive for prolintane plus cannabinoids, cocaine, nicotine, hydrocodone.

checked by claude-sonnet-4-6 · May 13, 2026

not supportedVisual hallucinations have been documented with prolintane use in two contexts: overdose settings and chronic therapeutic-dose combination with diphenhydramine^[5]88%

Not supported

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

Abstract (citation [4]) does not document visual hallucinations in any of the two described cases. Case 1 shows confusion/agitation; Case 2 shows fetal death. The hallucination documentation is in citation [6], not [4].

Case 1: 34yo male, confused and agitated... Case 2: 26yo female, intrauterine fetal death.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedVisual hallucinations have been documented with prolintane use in two contexts: overdose settings and chronic therapeutic-dose combination with diphenhydramine^[21]88%

Verified

Abstract confirms visual hallucinations with chronic therapeutic-dose prolintane + diphenhydramine combination. This citation supports the therapeutic-dose combination context specifically.

Young man developed visual hallucinations after 2 months of prolintane + diphenhydramine at therapeutic doses.

checked by claude-sonnet-4-6 · May 13, 2026

not supportedPsychosis is listed among overdose-associated outcomes.^[5]85%

Not supported

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

Abstract describes confusion and agitation (Case 1) and fetal death (Case 2). Psychosis is not explicitly documented or listed as an outcome in either case.

Case 1: 34yo male, confused and agitated.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedThe hallucinations observed with prolintane-diphenhydramine combination at therapeutic doses developed over a 2-month period and were attributed to pharmacological kindling — progressive sensitization of dopaminergic pathways producing hallucinatory experiences at doses that were initially well-tolerated.^[21]97%

Verified

Abstract directly confirms: visual hallucinations after 2 months, therapeutic doses, pharmacological kindling proposed as mechanism.

Young man developed visual hallucinations after 2 months of prolintane + diphenhydramine at therapeutic doses... Pharmacological kindling proposed.

checked by claude-sonnet-4-6 · May 13, 2026

not supportedInsomnia, nervousness, and irritability are documented side effects at therapeutic doses^[5]88%

Not supported

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

Abstract covers only two overdose/abuse cases (confusion/agitation and fetal death). Insomnia, nervousness, and irritability at therapeutic doses are not mentioned.

First US-documented cases of prolintane abuse. Case 1: 34yo male, confused and agitated. Case 2: 26yo female, intrauterine fetal death.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedDose-dependent REM sleep suppression is confirmed in controlled studies, and extended wakefulness at higher doses (15–30 mg) may precipitate sleep-deprivation-related psychological disturbance.^[9]90%

Verified

Abstract confirms dose-dependent REM suppression and increased awakenings at 15–30 mg. The sleep-deprivation psychological disturbance inference is reasonable from EEG-confirmed sleep disruption data.

Prolintane 15 and 30mg reduced REM sleep... Increased awakenings early in the night at higher doses. EEG-confirmed sleep disruption.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedLee et al. (2022) conducted the first systematic evaluation of prolintane's abuse potential in rodents:^[4]90%

Verified

Abstract describes a systematic multi-paradigm evaluation (locomotor activity, CPP, self-administration, drug discrimination, microdialysis) of prolintane abuse potential in rodents.

Prolintane increased locomotor activity, produced conditioned place preference, supported intravenous self-administration, and partially substituted for cocaine in drug discrimination.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedThe authors concluded that prolintane possesses "a certain level of abuse potential" comparable to cocaine at a moderate level.^[4]97%

Verified

Abstract directly confirms moderate abuse potential similar to cocaine.

Results indicate moderate abuse potential similar to cocaine at moderate level.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedThe historical discontinuation of prolintane from pharmaceutical markets was explicitly motivated by concerns about abuse liability.^[1]98%

Verified

Abstract directly confirms discontinuation due to abuse liability concerns.

its medical use was discontinued due to concerns about abuse liability.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedProlintane also inhibits NET and, at human transporters, releases serotonin via SERT substrate activity^[1]97%

Verified

Abstract confirms NET inhibition and hSERT-mediated serotonin efflux (SERT substrate activity).

Prolintane analogs display potent uptake inhibition at DAT and NET... Prolintane and analogs induced hSERT-mediated ionic currents and serotonin efflux.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedDeaths from tramadol combined with multiple serotonergic agents have been documented.^[24]97%

Verified

Abstract directly confirms death of a 36-year-old from seizure while taking tramadol combined with multiple serotonergic drugs (venlafaxine, trazodone, quetiapine).

Case report of death of 36-year-old from seizure activity while taking tramadol combined with venlafaxine, trazodone, and quetiapine.

checked by claude-sonnet-4-6 · May 13, 2026

not supportedDeaths from tramadol combined with multiple serotonergic agents have been documented.^[25]88%

Not supported

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

Abstract (citation [27]) documents serotonin syndrome/toxicity with tramadol polypharmacy but describes no death — the patient presented with symptoms (tremors, altered mentation, hallucinations, fever) but the abstract does not report a fatality.

Tramadol precipitated serotonin syndrome when added to citalopram + trazodone regimen in 79-year-old woman. Symptoms: tremors, altered mentation, hallucinations, fever, tachycardia, diaphoresis.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedmdma is a potent serotonin, dopamine, and norepinephrine releaser that can cause serotonin syndrome and hyperthermia at high doses^[26]97%

Verified

Abstract directly confirms MDMA as a potent releaser/reuptake inhibitor of serotonin, dopamine, and norepinephrine, and that acute toxic effects include serotonin syndrome and hyperthermia.

MDMA is a potent releaser/reuptake inhibitor of serotonin, dopamine, and norepinephrine. Acute toxic effects include serotonin syndrome (muscle rigidity, hyperreflexia, hyperthermia).

checked by claude-sonnet-4-6 · May 13, 2026

verifiedThe combination of prolintane and diphenhydramine at therapeutic doses produced visual hallucinations in one documented case after 2 months of concurrent use^[21]98%

Verified

Abstract directly confirms visual hallucinations after 2 months of prolintane + diphenhydramine at therapeutic doses.

Young man developed visual hallucinations after 2 months of prolintane + diphenhydramine at therapeutic doses.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedGiven prolintane's documented hERG channel inhibition in rodent models, combination with other QT-prolonging drugs (antiarrhythmics, certain antibiotics, antipsychotics, methadone) carries additive risk of ventricular arrhythmia.^[6]90%

Verified

Abstract confirms hERG inhibition and QT prolongation risk, from which the additive arrhythmia risk with other QT-prolonging drugs is a standard pharmacological inference.

QT prolongation and hERG potassium channel inhibition observed at certain concentrations — ventricular arrhythmia risk.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedCardiac conduction disorders (absolute): Prolintane inhibits the hERG potassium channel and prolongs the QT interval in rodent models^[6]98%

Verified

Abstract directly confirms hERG potassium channel inhibition and QT prolongation in rodents.

QT prolongation and hERG potassium channel inhibition observed at certain concentrations — ventricular arrhythmia risk.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedPregnancy (absolute): Prolintane was detected in a case of intrauterine fetal death^[5]98%

Verified

Abstract directly confirms Case 2: intrauterine fetal death with positive prolintane detection.

Case 2: 26yo female, intrauterine fetal death, positive for prolintane plus cannabinoids, cocaine, nicotine, hydrocodone.

checked by claude-sonnet-4-6 · May 13, 2026

partialHallucinations and psychosis are documented overdose outcomes, and hallucinations occurred at therapeutic doses in combination with diphenhydramine.^[21]82%

Partial

Abstract (citation [6]) confirms hallucinations at therapeutic doses with diphenhydramine combination. However, it does not document hallucinations or psychosis as overdose outcomes; the case involved therapeutic doses, not overdose.

Young man developed visual hallucinations after 2 months of prolintane + diphenhydramine at therapeutic doses.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedConcurrent serotonergic medication (relative to absolute, depending on agent): The SERT substrate activity at human transporters creates serotonin syndrome risk when combined with SSRIs, SNRIs, MAOIs, tramadol, or other serotonergic agents.^[1]90%

Verified

Abstract confirms SERT substrate activity (serotonin efflux) at human transporters. The serotonin syndrome risk with serotonergic co-medications is a standard pharmacological inference from this mechanism.

Prolintane and analogs induced hSERT-mediated ionic currents and serotonin efflux — classifying them as hybrid compounds at human monoamine transporters.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedCardiovascular disease (relative): While therapeutic doses (10–20 mg) produced minimal cardiovascular effects, the hERG inhibition data and dose-dependent risk profile warrant caution in individuals with pre-existing cardiovascular conditions.^[8]88%

Verified

Abstract confirms the minimal cardiovascular effects at 10–20 mg, which forms the basis of the conditional risk framing. The hERG data referenced comes from another study and is not disputed here.

Minimal cardiovascular effects (vs ephedrine which significantly raised BP and HR). Doses in 10-20mg range commonly used medically.

checked by claude-sonnet-4-6 · May 13, 2026

clinical evidence5 claims5verified

verifiedThe most informative controlled study of prolintane in humans is a double-blind, placebo-controlled comparison of single oral doses of prolintane HCl (10 mg and 20 mg) against ephedrine, fenfluramine, and phentermine in healthy medical student volunteers.^[8]95%

Verified

Abstract directly confirms double-blind placebo-controlled design, medical student subjects, 10 mg and 20 mg doses, and comparison with ephedrine.

Double-blind placebo-controlled study in medical students. Single oral doses of prolintane HCl 10 or 20 mg. Minimal cardiovascular effects (vs ephedrine which significantly raised BP and HR).

checked by claude-sonnet-4-6 · May 13, 2026

verifiedAt low doses (5–10 mg oral), prolintane reduced REM sleep during the first 2 hours after sleep onset without altering sleep latency or slow-wave sleep.^[20]98%

Verified

Abstract directly and completely confirms the claim word-for-word.

prolintane HCl 5 and 10mg reduced REM sleep in first 2h after sleep onset; no change in sleep latencies or slow wave sleep.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedAt higher doses (15–30 mg oral), prolintane significantly reduced total REM sleep — both delaying the first REM period and reducing cumulative REM time — while increasing awakenings during the early night and prolonging wakefulness in some subjects^[9]97%

Verified

Abstract directly confirms all elements: 15 and 30 mg, delayed first REM, reduced total REM, increased awakenings early in the night.

Prolintane 15 and 30mg reduced REM sleep (delayed first REM period, reduced total REM) in 6 healthy males. Increased awakenings early in the night at higher doses.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedA double-blind trial evaluated prolintane (as Katovit) combined with oxazepam against opipramol for depressive syndromes^[15]93%

Verified

PubMed record description directly confirms: double-blind study of prolintane (Katovit brand) + oxazepam for depressive syndromes vs opipramol.

No abstract available in PubMed record. Double-blind study of prolintane (Katovit brand) combined with oxazepam for depressive syndromes, compared with opipramol.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedKyle and Daley (2007) reported the first documented US cases of prolintane abuse:^[5]95%

Verified

Abstract explicitly confirms first US-documented cases of prolintane abuse.

First US-documented cases of prolintane abuse.

checked by claude-sonnet-4-6 · May 13, 2026

comparative pharmacology8 claims5verified2partial1not supported

verifiedIn drug discrimination paradigms, cumulative prolintane doses up to 10 mg/kg intraperitoneally produced only 38.57% cocaine-appropriate responding in cocaine-trained mice — a partial substitution indicating overlapping but non-identical discriminative stimulus properties^[4]98%

Verified

Abstract directly confirms 38.57% cocaine-appropriate responding at up to 10 mg/kg as partial substitution.

partially substituted for cocaine in drug discrimination (38.57% at up to 10 mg/kg).

checked by claude-sonnet-4-6 · May 13, 2026

verifiedAt therapeutic oral doses (10–20 mg), prolintane produced minimal cardiovascular effects in a controlled comparison with ephedrine, fenfluramine, and phentermine — each of which generated more pronounced blood pressure and heart rate changes^[8]92%

Verified

Abstract confirms minimal cardiovascular effects vs ephedrine (which significantly raised BP and HR). The full paper covers all three comparators; ephedrine is the one named in the abstract.

Minimal cardiovascular effects (vs ephedrine which significantly raised BP and HR).

checked by claude-sonnet-4-6 · May 13, 2026

verifiedThe critical differentiator is prolintane's hybrid mechanism — potent DAT/NET reuptake inhibition combined with SERT substrate activity (serotonin efflux) at human transporters^[1]97%

Verified

Abstract directly confirms the hybrid classification: potent DAT/NET inhibition and hSERT-mediated serotonin efflux.

Prolintane analogs display potent uptake inhibition at DAT and NET... Prolintane and analogs induced hSERT-mediated ionic currents and serotonin efflux — classifying them as hybrid compounds at human monoamine transporters.

checked by claude-sonnet-4-6 · May 13, 2026

partialPyrovalerone is the beta-keto derivative of prolintane — structurally identical except for a carbonyl group at the benzylic position^[16]78%

Partial

Abstract confirms pyrovalerone is '4-methyl-β-keto-prolintane', establishing the beta-keto relationship. However, the '4-methyl' modifier indicates an additional structural difference beyond the carbonyl alone, making 'structurally identical except for a carbonyl group' incomplete.

Pyrovalerone (4-methyl-β-keto-prolintane) is a synthetic cathinone.

checked by claude-sonnet-4-6 · May 13, 2026

not supportedProlintane's locomotor-stimulating effects were significant but less pronounced than methamphetamine at comparable doses^[4]88%

Not supported

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

Abstract confirms prolintane increased locomotor activity with moderate abuse potential, but compares to cocaine (not methamphetamine). No methamphetamine comparison is present.

Results indicate moderate abuse potential similar to cocaine at moderate level.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedThe authors characterized prolintane's abuse potential as moderate relative to cocaine.^[4]98%

Verified

Abstract directly confirms moderate abuse potential similar to cocaine.

Results indicate moderate abuse potential similar to cocaine at moderate level.

checked by claude-sonnet-4-6 · May 13, 2026

verifiedProlintane blocks transporter-mediated reuptake without inducing reverse transport — as demonstrated by the DOPAC enhancement pattern in rat brain following spiperone treatment^[7]95%

Verified

Abstract directly confirms DOPAC enhancement post-spiperone and reuptake inhibitor (not releaser) classification.

Prolintane enhanced increase in DOPAC (dopamine metabolite) in rats treated with spiperone... acting as a reuptake inhibitor rather than releaser.

checked by claude-sonnet-4-6 · May 13, 2026

partialThe serotonin-releasing activity at human SERT does introduce a release component, but this is restricted to the serotonergic system and has ≥10-fold lower potency than the catecholaminergic reuptake inhibition.^[1]78%

Partial

Abstract confirms SERT activity is weaker than DAT/NET and is serotonin-specific. However, the '≥10-fold' figure refers to hSERT vs rSERT species comparison, not SERT vs DAT potency comparison. The claim misattributes the 10-fold ratio.

SERT inhibitory potencies at least 10-fold weaker at hSERT vs rSERT... Prolintane and analogs induced hSERT-mediated ionic currents and serotonin efflux.

checked by claude-sonnet-4-6 · May 13, 2026

Coverage & Gaps

effect links

54 links · 53 approved · 28 audited1/54 with evidence basis

interactions

3 approved pairs0/3 graded

Research Trail

substance-article pipeline-v5 May 12, 2026

Research document (raw, unedited pipeline output)

# Research Output: Prolintane

---

## Chemical Identity

**Verified against PubChem (CID 14592) [Ref 20]:**

| Property | Value | Source |
|---|---|---|
| IUPAC name | 1-(1-phenylpentan-2-yl)pyrrolidine | PubChem CID 14592 |
| Molecular formula | C₁₅H₂₃N | PubChem / NCATS confirmed |
| Molecular weight | 217.35 g/mol | PubChem / NCATS confirmed |
| InChIKey | OJCPSBCUMRIPFL-UHFFFAOYSA-N | PubChem confirmed |
| CAS number | 493-92-5 | NCATS Inxight Drugs [Ref 20] |
| SMILES (canonical) | CCCC(Cc1ccccc1)N1CCCC1 | PubChem derived |
| WHO-ATC code | N06BX14 (psychostimulants) | NCATS Inxight Drugs [Ref 20] |
| UNII | EM4YZW677H | NCATS Inxight Drugs [Ref 20] |
| Stereochemistry | Racemic mixture (no specific active enantiomer identified) | NCATS Inxight Drugs [Ref 20] |

**Notes on the brief's seed data:**
- The brief lists no SMILES, molecular formula, molecular weight, InChIKey, or PubChem CID — all are confirmed above.
- The systematic name "1-(1-phenylpentan-2-yl)pyrrolidine" in the brief is confirmed by PubChem.
- The NCATS database SMILES entry contains a typographic error (C=C in phenyl ring notation); the correct canonical SMILES is CCCC(Cc1ccccc1)N1CCCC1.

**Brand names documented:** Katovit (Spain, FHER), Villescon (Europe, Boehringer Ingelheim), Catovit, Promotil [Ref 19].

---

## Pharmacology

### Mechanism of Action

Prolintane is classified as a norepinephrine-dopamine reuptake inhibitor (NDRI), acting primarily by blocking the dopamine transporter (DAT) and norepinephrine transporter (NET), thereby increasing synaptic concentrations of dopamine and norepinephrine. This mechanism is pharmacologically analogous to cocaine and methylphenidate, not amphetamine (Kastner et al. 2025 [Ref 1]; Fuller & Snoddy 1979 [Ref 10]).

Fuller & Snoddy (1979 [Ref 10]) established the reuptake inhibition mechanism by showing that prolintane markedly enhanced the dopamine metabolite DOPAC (3,4-dihydroxyphenylacetic acid) in rat brain after spiperone treatment — a pattern characteristic of DAT inhibitors (cocaine, methylphenidate) rather than DAT releasers (amphetamine).

The 2025 Kastner et al. study ([Ref 1]) using radiotracer flux assays in HEK293 cells and rat brain synaptosomes reports additional nuance:
- Prolintane is a **potent DAT and NET inhibitor**, with ≥10-fold weaker potency at SERT compared to DAT at human transporters.
- Critically, prolintane and its analogs **induce hSERT-mediated ionic currents and [³H]serotonin efflux** in cells expressing human SERT — classifying prolintane as a **hybrid compound** with SERT substrate activity at the human transporter.
- This human SERT releasing activity was **not observed in rat brain synaptosomes**, representing a significant species difference. This means prior rat-only studies underestimated the serotonergic activity of prolintane in humans.

**⚠️ FLAG — Mechanism discrepancy:** A 2002 case report (Paya et al. [Ref 6]) describes prolintane as inducing "dopamine release at the synaptic cleft" and diphenhydramine as a "dopamine reuptake inhibitor." This characterization reverses the established mechanisms. The weight of evidence (Fuller 1979, Lee 2022, Kastner 2025) supports DAT *reuptake inhibition* as the primary mechanism. Paya 2002's mechanistic framing appears outdated and reversed; it should not be cited as a primary pharmacology source. The clinical observation (hallucinogenic drug-drug interaction) remains valid.

### Receptor Binding Affinity

No substance-specific published Ki or IC50 values for prolintane at DAT, NET, or SERT were identified in the primary literature search. The 2025 Kastner study ([Ref 1]) reports assay data for prolintane and novel analogs but presents results primarily in terms of IC50 ratios and relative potency comparisons rather than providing standalone prolintane IC50 values in the abstract. The full paper would need to be consulted for exact values.

**Comparative context from closely related compounds:** Kolaczynska et al. (2021 [Ref 18]) profiled pyrovalerone-type cathinones (structural analogs) at human transporters in HEK293 cells — reporting DAT IC50 values of 0.02–8.7 µM and NET IC50 values of 0.03–4.6 µM across the class, with SERT activity absent below 10 µM in rat tissue. The related compound pyrovalerone is the beta-keto derivative of prolintane (Souders et al. 2019 [Ref 17]).

**⚠️ FLAG:** No standalone prolintane Ki/IC50 values confirmed from published literature. Generation agent should not cite specific numerical binding values without the full Kastner 2025 paper.

### Pharmacokinetics

No published human pharmacokinetic studies were found. The following data are absent from the primary literature:
- Oral bioavailability
- Peak plasma time (Tmax)
- Half-life (elimination t½)
- Volume of distribution
- Protein binding
- Human CYP enzyme involvement

**Animal metabolism data:** Yoshihara & Yoshimura (1974 [Ref 11]) conducted a foundational rat metabolism study of prolintane and assessed the pharmacological activity of metabolites in mice. No abstract was available; specific metabolites are not documentable from the PubMed record alone.

**Metabolic pathway (inferred from class):** Vickers & Polsky (2000 [Ref 12]) describe the biotransformation of pyrrolidine-containing compounds (including prolintane) to lactam metabolites. The proposed pathway involves:
1. Oxidation of the pyrrolidine nitrogen to an **iminium ion** intermediate
2. Oxidation to a **carbinolamine** intermediate
3. Oxidation by aldehyde oxidases (cytosolic molybdenum hydroxylases) or CYP450 enzymes to form the **lactam**

Species differences in lactam formation may arise from differences in aldehyde oxidase and CYP450 isozyme concentrations [Ref 12]. Specific CYP isozymes for prolintane are not established in human studies.

**⚠️ FLAG:** All pharmacokinetic data is absent from published human studies. Duration data in DB (onset 20-60 min, peak 2-3h, total 4-6h) appears to be derived from community consensus rather than controlled studies.

### Stimulant Effects Confirmed in Controlled Human Studies

Kuitunen et al. (1984 [Ref 7]) conducted a double-blind, placebo-controlled study comparing single oral doses of prolintane HCl (10 or 20 mg) to ephedrine, fenfluramine, and phentermine in healthy volunteer medical students:
- Prolintane produced **minimal cardiovascular effects** at therapeutic doses (10-20 mg) — in contrast to ephedrine which significantly raised BP and HR.
- Prolintane significantly improved performance on a sign recording test (cognitive performance task) at 2.5 hours post-dose (p<0.05).
- No significant change in tapping rate (motor speed) or digit span (working memory).

This study is notable as one of the only published controlled human dose trials for prolintane.

---

## History

### Discovery and Development

Prolintane was synthesized in the **1950s** as part of research into amphetamine analogs aimed at developing CNS stimulants. It was patented in Germany (DE 1088962, 1956) and the United Kingdom (GB 807835, 1959) by **Thomae**, a pharmaceutical company that was a predecessor to Boehringer Ingelheim [Ref 23].

**Commercialization:**
- **Boehringer Ingelheim** marketed prolintane in Europe as **Villescon** from the early 1960s, positioning it as a mild psychostimulant for fatigue and asthenia [Refs 19, 23].
- **FHER** (a Spanish pharmaceutical company) marketed it as **Katovit** in Spain from the 1960s onwards, combined with vitamins in orange-coated tablets; each tablet contained 200 mg prolintane and sold inexpensively (~€1.93/20 tablets) [Ref 5].
- Additional brand names included **Catovit** and **Promotil** [Ref 19].

**Clinical indications during active medical use:**
- ADHD
- Narcolepsy
- Fatigue and asthenia
- Orthostatic hypotension
- Depressive syndromes (combination with oxazepam studied in double-blind trial, Gmür & Angst 1977 [Ref 15])
- Countries of use included South Africa, Australia, and across Europe [Ref 4, Ref 19].

**Withdrawal from markets:**
- Katovit was **withdrawn in Spain in 2001** due to safety and abuse concerns [Ref 19, 23].
- Medical use was discontinued more broadly due to abuse liability concerns (Kastner et al. 2025 [Ref 1]).

**Emergence as a recreational/rave drug:**
- Prolintane's inexpensive OTC availability in Spain made it accessible for recreational use at European rave parties. Gaulier et al. (2002 [Ref 5]) documented its use at rave parties in southwest France where Katovit tablets were sold as a stimulant.
- The first medically documented cases of US abuse were reported by Kyle & Daley (2007 [Ref 4]).
- Since the mid-2010s, prolintane has appeared on research chemical markets as a psychostimulant NPS (Napoletano et al. 2020 [Ref 16]).

### WADA/Anti-Doping Status

Prolintane is listed as a **prohibited stimulant by WADA** (S6 Stimulants category) and **banned by the NCAA** (Docherty 2008 [Ref 13]; WADA Prohibited List [Ref 24]).

---

## Subjective Effects

### From Controlled Human Studies

**Cognitive effects (Kuitunen et al. 1984 [Ref 7]):**
- Improved sign recording performance (cognitive throughput) at 2.5 hours
- Minimal mental activity changes on self-rating checklist at 10-20 mg
- No significant change in memory, learning, concentration on digit span test

**Sleep effects (Nicholson et al. 1980 [Refs 8, 9]):**
- Prolintane HCl 5-10 mg: Reduced REM sleep in first 2 hours after sleep onset; no changes in sleep latency or slow-wave sleep [Ref 9]
- Prolintane 15-30 mg: Significantly reduced REM sleep (both delayed first REM period and reduced total REM); increased awakenings in early night; prolonged wakefulness in some subjects [Ref 8]
- These studies confirm **dose-dependent wakefulness promotion** and **REM suppression** as established pharmacodynamic effects

### From Case Reports and Clinical Observations

**Adverse subjective effects at high doses or in combination:**
- Confusion, agitation, inability to follow commands (Kyle & Daley 2007 [Ref 4])
- Visual hallucinations following 2 months of prolintane + diphenhydramine at therapeutic doses (Paya et al. 2002 [Ref 6])
- Hallucinations, psychosis reported with overdose (Kyle & Daley 2007 [Ref 4])

**Side effects noted at therapeutic doses (historical prescribing literature):**
- Insomnia, nervousness, irritability (Kyle & Daley 2007 [Ref 4])
- Dizziness (NCATS Inxight [Ref 20])

**Effect profile taxonomy note:** The 28 seed effects in the DB (all lacking intensity/frequency values) are consistent with the published pharmacology — stimulation, wakefulness, appetite suppression, focus enhancement, cognitive euphoria, compulsive redosing urge, abnormal heartbeat, anxiety, paranoia, thought acceleration, etc. are all plausible for an NDRI stimulant. However, **no controlled studies have formally characterized the full subjective effect profile** as a comparative or quantitative dataset.

---

## Safety & Toxicity

### Cardiovascular Toxicity

Jeong et al. (2023 [Ref 3]) evaluated prolintane in mice and rats and documented:
- **QT interval prolongation** at certain concentrations — indicating risk of ventricular arrhythmia
- **hERG potassium channel inhibition** — the canonical biomarker for drug-induced QT prolongation
- **No direct myocardial cytotoxicity** confirmed at tested concentrations
- Findings indicate prolintane "cannot be excluded" from causing ventricular arrhythmia risk

This is the most direct safety study for prolintane and it is conducted in rodents; human cardiac safety data is absent.

### Neurotoxicity

Jeong et al. (2023 [Ref 3]) also documented:
- **Shortened IBA-1 (microglial marker) length** in brain tissue following prolintane administration — interpreted as a marker of microglial activation/neuroinflammation potentially disrupting synaptic contacts
- **Reduced motor coordination** in rodents (both mice and rats)

### Overdose Profile

Kyle & Daley (2007 [Ref 4]) report that overdoses of prolintane may cause:
- Hallucinations
- Psychosis
- Death

Documented human cases in this paper include:
1. 34-year-old male with confusion, agitation, inability to follow commands (concurrent amitriptyline, nortriptyline, nicotine, prolintane — polydrug context)
2. 26-year-old female with intrauterine fetal death and spontaneous delivery (concurrent cannabinoids, cocaine, nicotine, hydrocodone, prolintane — heavy polydrug context)

Both cases involved polysubstance use; prolintane's individual contribution to the adverse events cannot be isolated.

### Toxicity Ratings (Seed Data Review)

The brief notes: "Acute: moderate; Chronic: moderate; Notes: Inferred from pharmacological class — not sourced from literature. Review recommended."

**⚠️ FLAG (Safety-Critical):** These toxicity ratings are explicitly flagged as inferred, not source-confirmed. No LD50 data for prolintane in humans or animals was found in the literature. The rodent cardiotoxicity data (hERG inhibition, QT prolongation) and the reported overdose deaths are consistent with a "moderate" acute toxicity rating, but this remains class-level inference. Generation agent should preserve the "inferred" caveat.

### Detection

Prolintane is **not detected by routine immunoassay urine drug screens**. Detection requires gas chromatography-mass spectrometry (GC-MS) (Kyle & Daley 2007 [Ref 4]). This is clinically important: clinicians should be aware that standard tox screens will miss prolintane intoxication.

---

## Harm Reduction

Based on available published evidence:

1. **Standard drug screens will not detect prolintane** — GC-MS is required (Kyle & Daley 2007 [Ref 4]). This has implications for emergency management: clinicians should request expanded toxicology panels when prolintane is suspected.

2. **QT prolongation risk**: Prolintane inhibits the hERG potassium channel (Jeong 2023 [Ref 3]). Users with pre-existing cardiac conditions, electrolyte abnormalities, or taking other QT-prolonging drugs are at elevated risk.

3. **Diphenhydramine combination is documented as dangerous**: The combination of prolintane + diphenhydramine at therapeutic doses caused visual hallucinations in one documented case over a 2-month period, attributed to pharmacological kindling via synergistic dopaminergic excess (Paya et al. 2002 [Ref 6]).

4. **No published overdose antidote or reversal agent** specific to prolintane was identified. Emergency management should follow general stimulant toxidrome protocols.

5. **Cardiovascular monitoring**: Given QT prolongation risk, cardiac monitoring (ECG) is warranted in presentations involving prolintane, particularly in polydrug contexts.

6. **Pregnancy**: Prolintane was detected in a case of intrauterine fetal death (Kyle & Daley 2007 [Ref 4]). While polydrug use prevents causal attribution, prolintane is not safe to assume benign in pregnancy. No published reproductive safety data exists.

---

## Tolerance & Dependence

### Animal Data

Lee et al. (2022 [Ref 2]) conducted the first systematic behavioral pharmacology evaluation of prolintane's abuse potential in rodents:
- **Locomotor sensitization**: Prolintane (10-20 mg/kg IP) significantly increased locomotor activity, though to a lesser degree than methamphetamine
- **Striatal dopamine**: Single injection at 20 mg/kg IP significantly increased extracellular dopamine in the striatum (in vivo microdialysis), implicating the mesolimbic pathway
- **Conditioned place preference (CPP)**: Significant drug-paired place preference at both 10 and 20 mg/kg — confirming rewarding properties
- **Intravenous self-administration**: Mice self-administered prolintane at 4 mg/kg/infusion with higher infusion rates and active lever presses than controls
- **Drug discrimination**: Cumulative prolintane doses (up to 10 mg/kg) partially substituted for cocaine in a cocaine-trained discrimination paradigm (38.57% cocaine-appropriate responding)

The authors concluded prolintane has "a certain level of abuse potential" similar to cocaine at a moderate level [Ref 2].

### Human Dependence Data

**No published human dependence studies were found.** The historical discontinuation of prolintane from medical markets was explicitly due to "concerns about abuse liability" (Kastner et al. 2025 [Ref 1]), confirming that the abuse potential was recognized clinically.

### Cross-Tolerance

No published cross-tolerance studies for prolintane were found. Given its DAT-inhibiting mechanism similar to cocaine, cross-tolerance with cocaine and other NDRI stimulants (methylphenidate) is pharmacologically expected but not experimentally confirmed.

### Withdrawal

No withdrawal characterization studies for prolintane were identified in the published literature. As an NDRI, post-use dopaminergic deficit states (fatigue, anhedonia, dysphoria) are expected by analogy with cocaine and methylphenidate — but substance-specific withdrawal data is absent.

---

## Interactions

### Tramadol (DB rating: "lethal")

**No prolintane-specific tramadol interaction case report was found in the published literature.**

The "lethal" rating is consistent with class-level pharmacology:
- Tramadol is a weak opioid that also inhibits serotonin and norepinephrine reuptake (NET inhibitor)
- Prolintane also inhibits NET, and the 2025 Kastner study confirms it has SERT substrate activity (serotonin-releasing) at human transporters [Ref 1]
- The combination could produce **serotonin syndrome** via combined serotonergic excess (NET inhibition + potential serotonin release)
- Tramadol also lowers seizure threshold — which may be compounded by stimulant use
- Deaths from tramadol + multiple serotonergic drugs have been documented (Ripple et al. 2000 [Ref 26]; Ruiz de Villa et al. 2021 [Ref 27])

**⚠️ FLAG (Safety-Critical):** The "lethal" interaction rating is not directly confirmed by a published prolintane+tramadol case report. The rating is supported by class-level pharmacological mechanism. Generation agent should note: "No prolintane-specific case reports found; risk is mechanistically supported by combined serotonergic effects and documented tramadol fatality cases with serotonergic polypharmacy."

### MDMA (DB rating: "dangerous")

**No prolintane-specific MDMA interaction study was found.**

Mechanistic risk:
- MDMA is a potent serotonin/dopamine/norepinephrine releaser and can cause serotonin syndrome and hyperthermia at high doses (de la Torre et al. 2004 [Ref 22])
- Combined with prolintane (DAT/NET inhibitor; human SERT substrate), the combination would be expected to substantially amplify cardiovascular strain (elevated BP, tachycardia) and serotonergic activity
- Both substances raise body temperature; hyperthermia risk is compounded in hot environments (raves, clubs)

**⚠️ FLAG:** "Dangerous" rating for MDMA is supported by class-level pharmacology; no prolintane-specific study found.

### Alcohol (DB rating: "unknown")

No published data found on prolintane-alcohol interaction. Rating of "unknown" is appropriate.

### Diphenhydramine (documented case report)

The combination of prolintane + diphenhydramine at therapeutic doses produced visual hallucinations in one documented case after 2 months of combined use (Paya et al. 2002 [Ref 6]). The proposed mechanism is synergistic dopaminergic excess. This interaction is not listed in the DB and represents a gap in the current contraindication data.

---

## Legal Status

| Jurisdiction | Status | Notes |
|---|---|---|
| United States | Not scheduled under CSA; not FDA-approved | Banned by WADA and NCAA for sport competition |
| United Kingdom | Covered by Psychoactive Substances Act 2016 | Not specifically scheduled under Misuse of Drugs Act 1971; PSA makes production/supply illegal |
| Australia | Schedule 4 (Prescription Only) | Formerly prescribed; now prescription-only under Therapeutic Goods Act |
| Germany | Prescription-only | Anlage 1 AMVV (Arzneimittelverschreibungsverordnung) |
| Spain | Withdrawn from market | Katovit withdrawn 2001; no longer available |
| WADA | Prohibited in competition | S6 Stimulants list |

Sources: [Ref 19, 21, 24]. These are web-retrieved sources — the exact current scheduling status in each jurisdiction should be verified against official government databases before publication.

**⚠️ FLAG (Verification needed):** UK and Australian scheduling status retrieved from secondary web sources (Wikipedia, PsychonautWiki). Legal status can change. Before publishing, verify:
- Australia: whether prolintane remains Schedule 4 or has been moved to Schedule 9 (prohibited)
- UK: confirm PSA 2016 applies (or any subsequent specific scheduling)
- Canada: No Canadian scheduling data found — this jurisdiction should be investigated before article publication

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## Clinical Trials

No clinical trials were found on ClinicalTrials.gov for prolintane. The compound has no active or registered trials.

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## Community Feedback Analysis

No community feedback was submitted for prolintane. The Part A2 section of the brief was empty.

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## Gaps & Flags

### Critical Safety Gaps
1. **⚠️ SAFETY-CRITICAL — Toxicity ratings unverified:** The seed data toxicity ratings ("Acute: moderate; Chronic: moderate") are explicitly noted as "inferred from pharmacological class." No published LD50 or systematic toxicology data for prolintane in humans was found. These values require editorial review before publication.

2. **⚠️ SAFETY-CRITICAL — Tramadol interaction:** The "lethal" interaction rating for Tramadol has no prolintane-specific case report. Mechanistically supported but not directly evidenced. Generation agent should explicitly state the evidential basis.

3. **⚠️ SAFETY-CRITICAL — MDMA interaction:** The "dangerous" rating is class-level inference only. No prolintane+MDMA study found.

### Pharmacology Gaps
4. **No human pharmacokinetic data:** Half-life, bioavailability, Tmax, CYP enzyme involvement, and protein binding are all undocumented for humans. Duration data in DB is community-consensus-derived.

5. **No standalone prolintane Ki/IC50 values confirmed:** Specific binding affinity numbers for prolintane at DAT, NET, SERT should not be cited without access to the full Kastner 2025 paper tables.

6. **Species difference in SERT activity:** Prolintane shows human SERT substrate activity (serotonin-releasing) not seen in rat synaptosomes (Kastner 2025 [Ref 1]). Rat-only preclinical data may underestimate serotonergic risk in humans. This is a clinically significant finding.

7. **Mechanism discrepancy in 2002 case report:** Paya et al. (2002 [Ref 6]) incorrectly characterize prolintane as a dopamine *releaser* rather than reuptake inhibitor, and diphenhydramine as a dopamine reuptake inhibitor. The clinical observation is valid; the mechanistic framing is outdated. Generation agent should correct this.

### Regulatory Gaps
8. **Canadian legal status not found:** No data was found for prolintane's status under Canada's CDSA or provincial pharmacy regulations. This should be researched before publication.

9. **Australian current scheduling needs verification:** Source indicates Schedule 4; unclear if this has changed to Schedule 9 given recreational abuse concerns.

### Data Gaps for Structured Fields
10. **No published withdrawal characterization** for prolintane — the DB "dependence data" field will need to be marked as class-inference.

11. **No active enantiomer identified:** Prolintane is marketed as a racemate; no literature was found establishing differential activity of enantiomers.

12. **Diphenhydramine interaction not in DB:** The documented interaction (Paya 2002) with diphenhydramine causing hallucinations should be considered for addition to the interactions table.

13. **Dose data in DB matches PsychonautWiki community consensus** — no controlled human dose-response study with pharmacokinetic monitoring was found to verify these ranges.

Prolintane

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