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psx:substance/a-php/value/tolerance@1

valuereferenced by edges — no row of its own

derived from · upstream

  • derived_fromtolerancepsx:substance/a-php/proposal/tolerance/913f90be-fa08-4744-bddd-7b52590ebe25

feeds · downstream

none recorded

Closure of psx:substance/a-php/value/tolerance@1: 1 upstream, 0 downstream.

psx:substance/a-php/value/tolerance@1
└─ derived_from  proposal/tolerance/913f90be-fa08-4744-bddd-7b52590ebe25  tolerance

indented by distance from this node, not by parentage

1Provenance card

the boundary, as counts

Sources

2421 with DOI

7 strong · 11 moderate · 6 weak

Compilations

12026-04-28T04:29:04.978Z

pipeline-v5 · prompt hash not recorded — run predates 2026-09

Decisions

57last ruled 2026-06-04

0 awaiting a ruling

Issued documents

42026-10-19T20:30:22.277Z

notice · info card · emergency

Searches

183 with no results

queries and counts on the build

Claims checked

8969 supported

69 supported · 20 not

Correspondence

0received

consent field ships in Phase 4

Edges

290

derivations recorded for this entity

Complete over 24 sources, 1 compilation, and 57 decisions.Not here: the private journal (never).Working material — drafts, discards, unsupported claims — is listed below and readable on the working page.Cite: psychedex.org/substances/a-php/archive

2Build

one panel per compilation run

generation run 2026-04-28

70 min completedmodel pipeline-v5plan not recordedrun/b7049f84…

Selection

results seen62
selected by the model40
consumed as sources24

Verification

claims checked89
supported62
partially supported7
not supported3
inconclusive17
  • record
  • seen / partial
  • working

The model's own caveats

  • sources_silent_on_taper
  • no_controlled_human_dependence_data

Reproduce

inputs
24 source keys (listed under Sources)
plan
not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
model
pipeline-v5
streams
none — agent transcripts are persisted from 2026-09 onward
18 searches — query, source, results, what was kept and why
18 searches for this run
#sourcequeryseenkeptrationale
1PubChemalpha-PHP11Primary chemical identity verification
2PubMedalpha-pyrrolidinohexanophenone metabolism metabolites human urine93Directly characterize α-PHP metabolism in humans
3OpenAlexalpha-PHP Schedule I controlled substance legal DEA31Contains specific legal scheduling information
4OpenAlexalpha-PHP pyrrolidinohexanophenone synthetic cathinone105High citation counts and relevance to A-PHP pharmacology and toxicology
5ClinicalTrials.gov · absencealpha-PHP pyrrolidinohexanophenone00No results
6PubMedalpha-PHP pyrrolidinohexanophenone pharmacology158All directly relevant to A-PHP pharmacology, toxicology, or clinical cases
7PsychonautWikiA-PHP dosage duration effects legal status12Cross-reference for dose/duration data matching existing DB values
8OpenAlexalpha-PHP neural stem progenitor cell death cytotoxicity11Unique neurotoxicity data specific to α-PHP in neural stem cells
9UNODC LSSalpha-PHP substance details11Official UNODC database; confirms chemical identity and scheduling
10Web searchalpha-PHP UK Misuse of Drugs Act legal status Australia52Legal status data for major jurisdictions
11WHO ECDD Repositoryalpha-PHP ECDD assessment11Official WHO assessment; authoritative for scheduling and pharmacology context
12Federal Register / Webalpha-PHP DEA Schedule I scheduling date32Establishes definitive US legal scheduling history for α-PHP
13OpenAlexSimmler Liechti cathinone monoamine transporter selectivity54Landmark papers establishing pyrovalerone cathinone pharmacological class; all have direct relevance to α-PHP mechanism of action
14Multiple sources · absencealpha-PHP IC50 DAT dopamine transporter specific binding affinity00No specific α-PHP IC50 data found; must flag in Gaps section
15PubMed · absencetramadol stimulant cathinone interaction fatal toxicity00No specific published evidence found; seed data 'lethal' interaction with tramadol cannot be verified from published literature
16Web searchalpha-PHP Canada Australia Japan scheduling legal status35Legal status data for major jurisdictions
17Multiple APIs and WebVerify chemical identity, SMILES, CAS, InChIKey for alpha-PHP33Chemical identity fully verified and corrects all seed data gaps
18Multiple sourcesVerify dose/duration data against published literature11No published controlled dosing study to contradict seed data; values retained
89 claims by section — every cited sentence, checked against its source
safety24 · 17 ok
  • The acute toxidrome documented across clinical case reports and poison control data comprises CNS alterations (psychomotor agitation, hallucinations, paranoid delusions, aggression), cardiovascular effects (tachycardia, tachypnoea, hypertension), hyperthermia, and rhabdomyolysissupported

    Clinical cases showed CNS toxidromes (psychomotor agitation, tremors, hallucinations), cardiovascular signs (tachycardia, tachypnoea), hyperthermia, rhabdomyolysis. j.drugalcdep.2025.112596

  • Claim in safety — inconclusiveinconclusiveworking →

  • Claim in safety — inconclusiveinconclusiveworking →

  • Prolonged psychosis lasting 3 or more days has been documented, consistent with the compound's estimated 37-hour serum half-life.supported

    Psychotic symptoms resolved by day 3. Serum elimination half-life 37 h. bkx080

  • Tachycardia, hypertension, and tachypnoea are consistently reported across clinical casespartially supported

    Clinical cases showed cardiovascular signs (tachycardia, tachypnoea). j.drugalcdep.2025.112596

  • Rhabdomyolysis — skeletal muscle breakdown releasing myoglobin into the bloodstream — is documented in α-PHP clinical intoxicationssupported

    Clinical cases showed... rhabdomyolysis. j.drugalcdep.2025.112596

  • In vitro studies in murine neural stem/progenitor cells demonstrated dose-dependent cytotoxicity at α-PHP concentrations of 25–2000 μM, with activation of apoptotic, autophagic, and necroptotic cell death pathways and ultrastructural damage visible by transmission electron microscopysupported

    α-PHP induced dose-dependent decrease in viability, proliferation, and clonal capability of murine NSPCs at 25–2000 μM. Apoptotic/autophagic/necroptotic pathway activation observed. Ultrastructural alterations. biology12091225

  • Metabolites generated through hepatic metabolic activation demonstrate mutagenic potential in the micronucleus assaysupported

    metabolites with metabolic activation showed mutagenic potential. ijms22126320

  • A fetal death has been associated with maternal use of MDPHP and α-PHPsupported

    Case report of fetal death associated with use of MDPHP and α-PHP. 15563650.2018.1502443

  • Claim in safety — inconclusiveinconclusiveworking →

  • In the Fujita case report, psychosis persisted for 3 days following presentation, correlated with the prolonged serum half-lifesupported

    Psychotic symptoms resolved by day 3. Serum elimination half-life 37 h. bkx080

  • Claim in safety — inconclusiveinconclusiveworking →

  • Psychomotor agitation, aggressive behavior, and impaired judgment are consistently documented in clinical presentationssupported

    Clinical cases showed CNS toxidromes (psychomotor agitation, tremors, hallucinations). j.drugalcdep.2025.112596

  • ICSS in rats: 1.0 and 3.2 mg/kg i.p. facilitated ICSS responding, comparable to cocaine at 10 mg/kgsupported

    Doses of 1.0 and 3.2 mg/kg α-PHP facilitated ICSS responding similar to cocaine (10 mg/kg). j.etdah.2021.100004

  • Brain reward thresholds decreased dose-dependently in female ratssupported

    ICSS brain reward thresholds decreased dose-dependently. j.drugalcdep.2021.108910

  • Abuse liability assessed as equivalent to α-PVPsupported

    Abuse liability equivalent across all three α-pyrrolidino-phenone cathinones. j.drugalcdep.2021.108910

  • Claim in safety — inconclusiveinconclusiveworking →

  • The most salient interaction risk with α-PHP arises from its nearly universal co-use with other substances in real-world settings: 90% of confirmed cases in the largest series involved polydrug co-ingestionpartially supported

    60% opiates, 35% benzodiazepines, 30% cannabinoids, 20% cocaine co-use. bkac057

  • Claim in safety — inconclusiveinconclusiveworking →

  • Clinical management follows pyrovalerone cathinone class protocols extrapolated from MDPV experience: supportive care with IV benzodiazepines as first-line for agitation and seizure prevention, IV fluids for rhabdomyolysis, and close cardiovascular and temperature monitoringsupported

    Treatment: IV benzodiazepines, supportive care, ICU monitoring. j.amjmed.2012.02.019

  • Pre-existing cardiovascular disease — including hypertension, coronary artery disease, and arrhythmia — represents the primary absolute contraindication, given the consistent documentation of sympathomimetic cardiovascular stress across all clinical case reports.supported

    Clinical cases showed cardiovascular signs (tachycardia, tachypnoea), hyperthermia, rhabdomyolysis. j.drugalcdep.2025.112596

  • Psychotic spectrum disorders and bipolar disorder are absolute contraindications: α-PHP's dopaminergic potentiation directly exacerbates psychotic symptomatology, and the documented multi-day psychosis duration makes acute episodes potentially severe and prolonged.supported

    Psychotic symptoms resolved by day 3. bkx080

  • Pregnancy is absolutely contraindicated: fetal death has been documented in association with α-PHP use, and in utero transfer is confirmed by neonatal meconium testing.partially supported

    Case report of fetal death associated with use of MDPHP and α-PHP. First report of such outcome. 15563650.2018.1502443

  • Claim in safety — inconclusiveinconclusiveworking →

pharmacology20 · 17 ok
  • Monoamine efflux: absent — α-PHP does not act as a releasing agentsupported

    None induce monoamine efflux. ijms22158277

  • Serum concentration data fitted a two-compartment pharmacokinetic model with an estimated serum elimination half-life of 37 hourssupported

    Two-compartment model; serum elimination half-life 37 h. bkx080

  • α-PHP is a potent dopamine transporter (DAT) and norepinephrine transporter (NET) reuptake inhibitor that blocks monoamine uptake without inducing monoamine effluxsupported

    Pyrovalerone and MDPV classified as highly potent, selective DA and NA transporter inhibitors that do not evoke monoamine release (unlike amphetamines). j.1476-5381.2012.02145.x

  • α-PHP is a potent dopamine transporter (DAT) and norepinephrine transporter (NET) reuptake inhibitor that blocks monoamine uptake without inducing monoamine effluxsupported

    Pyrovalerone cathinones act as selective DA and NA uptake inhibitors without monoamine efflux. smw.2015.14043

  • This pure uptake inhibition mechanism — pharmacologically analogous to cocaine and MDPV rather than to amphetamine-type releasing agents — places α-PHP firmly within the pyrovalerone subclass of synthetic cathinones.supported

    Pyrovalerone and MDPV classified as highly potent, selective DA and NA transporter inhibitors that do not evoke monoamine release (unlike amphetamines). j.1476-5381.2012.02145.x

  • Claim in pharmacology — inconclusiveinconclusiveworking →

  • Davies and colleagues describe it qualitatively as "at least as potent as α-PVP as a dopamine transporter reuptake inhibitor" based on synaptosomal assay datasupported

    Using a synaptosomal assay, α-PHP is at least as potent as α-PVP as a DAT reuptake inhibitor. acschemneuro.3c00156

  • The class range for second-generation pyrovalerone cathinones spans DAT IC₅₀ = 0.02–8.7 μM and NET IC₅₀ = 0.03–4.6 μM.supported

    All pyrovalerone cathinones: DAT IC50=0.02–8.7 μM, NET IC50=0.03–4.6 μM. ijms22158277

  • SERT: no significant activity at concentrations below 10 μMsupported

    no SERT activity <10 μM. ijms22158277

  • SERT: no significant activity at concentrations below 10 μMsupported

    Pyrovalerone and MDPV classified as highly potent, selective DA and NA transporter inhibitors. j.1476-5381.2012.02145.x

  • Claim in pharmacology — inconclusiveinconclusiveworking →

  • In a 29-case forensic series, serum α-PHP concentrations ranged from 1 to 83 ng/mL (mean 40 ng/mL, median 36 ng/mL; median age 39.5 years, 90% male).supported

    Serum concentrations 1–83 ng/mL (mean 40, median 36). Median age 39.5 yr, 90% male. bkac057

  • Bassi and colleagues studied pharmacokinetic sex differences in CD-1 mice following intraperitoneal administration at 30 mg/kgsupported

    Evaluates acute effects of α-PHP (0.1–30 mg/kg i.p.) in CD-1 male and female mice. Male mice showed higher plasma levels and different metabolite elimination. j.drugalcdep.2025.112596

  • Primary hepatic metabolism involves multiple cytochrome P450 enzymes:supported

    CYP enzymes involved: CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4. For α-PHP: CYP1A2, CYP2C9, CYP2C19 mainly involved. dta.2355

  • Phase I metabolic pathways include hydroxylation of the pyrrolidine ring, lactam formation (oxidation of the pyrrolidine nitrogen to produce ring-opened products), and alkyl chain hydroxylation.supported

    Phase I: hydroxy metabolites and lactams. dta.2355

  • Claim in pharmacology — inconclusiveinconclusiveworking →

  • In authentic human urine, 11 phase I metabolites and 5 phase II glucuronide conjugates have been identifiedsupported

    11 phase I + 5 phase II glucuronide metabolites identified. bkac057

  • Human hepatocyte incubation studies confirmed dihydroxy-pyrrolidinyl-α-PHP as the major metabolite and additionally identified α-PHP hexanol, α-PHP 2'-keto-pyrrolidinyl-hexanol, and α-PHP 2'-keto-pyrrolidinyl as prominent metabolic products.supported

    Identified α-PHP dihydroxy-pyrrolidinyl, hexanol, 2'-keto-pyrrolidinyl-hexanol, and 2'-keto-pyrrolidinyl as markers of use. Identified novel major metabolite α-PHP dihydroxy-pyrrolidinyl. ijms22010230

  • However, metabolites generated through extrinsic metabolic activation demonstrated mutagenic potential in the micronucleus assaysupported

    metabolites with metabolic activation showed mutagenic potential. ijms22126320

  • No significant increase in reactive oxygen species (ROS) was observed from the parent compoundsupported

    No significant ROS increase. ijms22126320

summary11 · 10 ok
  • Claim in summary — inconclusiveinconclusiveworking →

  • The compound is the direct one-carbon α-alkyl chain homolog of α-PVP ("flakka"), extending the n-propyl chain to n-butyl, and produces intense psychomotor stimulation with a serum elimination half-life estimated at 37 hours from a single case report.supported

    Two-compartment model; serum elimination half-life 37 h. bkx080

  • The pyrrolidinophenone scaffold was first patented in the United States in 1967 but never marketed pharmaceutically. α-PHP appeared on the Japanese illicit drug market in 2014 as a scheduling-evasion successor to α-PVPsupported

    α-PHP appeared on Japanese illicit drug market in 2014. life14040429

  • α-PHP acts as a selective DAT/NET reuptake inhibitor with no significant serotonin transporter activity at concentrations below 10 μM and no monoamine-releasing propertiessupported

    All pyrovalerone cathinones: DAT IC50=0.02–8.7 μM, NET IC50=0.03–4.6 μM, no SERT activity <10 μM. None induce monoamine efflux. ijms22158277

  • α-PHP acts as a selective DAT/NET reuptake inhibitor with no significant serotonin transporter activity at concentrations below 10 μM and no monoamine-releasing propertiessupported

    Pyrovalerone and MDPV classified as highly potent, selective DA and NA transporter inhibitors that do not evoke monoamine release (unlike amphetamines). j.1476-5381.2012.02145.x

  • No discrete IC₅₀ value has been published for α-PHP specifically, though it is described as "at least as potent as α-PVP" at the DATsupported

    Using a synaptosomal assay, α-PHP is at least as potent as α-PVP as a DAT reuptake inhibitor. acschemneuro.3c00156

  • Clinical presentations include agitation, paranoid ideation, hallucinations, tachycardia, and hyperthermiapartially supported

    39-year-old male presented with hallucinations and delusion. Psychotic symptoms resolved by day 3. bkx080

  • Clinical presentations include agitation, paranoid ideation, hallucinations, tachycardia, and hyperthermiasupported

    Clinical cases showed CNS toxidromes (psychomotor agitation, tremors, hallucinations), cardiovascular signs (tachycardia, tachypnoea), hyperthermia, rhabdomyolysis. j.drugalcdep.2025.112596

  • Cardiovascular toxicity — tachycardia, hypertension, and rhabdomyolysis — is documented across clinical case seriespartially supported

    Clinical cases showed cardiovascular signs (tachycardia, tachypnoea), hyperthermia, rhabdomyolysis. j.drugalcdep.2025.112596

  • Preclinical abuse liability is equivalent to cocaine in intracranial self-stimulation assays, and the WHO ECDD concluded that the mechanism "suggests it is highly likely to produce a state of dependence similar to amphetamine"partially supported

    Doses of 1.0 and 3.2 mg/kg α-PHP facilitated ICSS responding similar to cocaine (10 mg/kg). j.etdah.2021.100004

  • In vitro neurotoxicity data show dose-dependent neural stem cell death via apoptotic, autophagic, and necroptotic pathways, though at concentrations far exceeding measured human serum levelssupported

    α-PHP induced dose-dependent decrease in viability, proliferation, and clonal capability of murine NSPCs at 25–2000 μM. Apoptotic/autophagic/necroptotic pathway activation observed. biology12091225

history8 · 7 ok
  • The following year brought two critical developments: the first documented fetal death associated with α-PHP and MDPHP use, and the WHO Expert Committee on Drug Dependence (ECDD) 42nd meeting recommendation for Schedule II placement under the 1971 Convention on Psychotropic Substances.partially supported

    Case report of fetal death associated with use of MDPHP and α-PHP. First report of such outcome linking these synthetic cathinones to fetal mortality. 15563650.2018.1502443

  • The first clinical attention to the hexanophenone variant came indirectly: in 2011, Sauer and colleagues published the first acute poisoning case report involving 4'-methyl-α-pyrrolidinohexanophenone (MPHP), a close structural analog of α-PHP carrying a 4'-methyl ring substitutionsupported

    First report of acute poisoning involving MPHP, the 4'-methyl homolog of α-PHP. j.forsciint.2011.02.026

  • α-PHP itself first appeared on the Japanese illicit drug market in 2014supported

    α-PHP appeared on Japanese illicit drug market in 2014. life14040429

  • This molecular cat-and-mouse dynamic has been a defining feature of the synthetic cathinone market since the scheduling of mephedrone and MDPV.supported

    Most newly developed cathinones are analogs replacing once-popular compounds after scheduling. s11419-022-00639-5

  • Claim in history — inconclusiveinconclusiveworking →

  • The first published human toxicokinetics data came from Japan in 2018, when Fujita and colleagues reported a case of prolonged psychosis with serial serum concentration measurementssupported

    Human toxicokinetics case report: 39-year-old male presented with hallucinations and delusion. Serum α-PHP 175 ng/mL on arrival. Two-compartment model; serum elimination half-life 37 h. bkx080

  • The most comprehensive clinical case series (29 confirmed cases) and human metabolite identification study was published in 2023supported

    29-case series with analytically confirmed α-PHP. 11 phase I + 5 phase II glucuronide metabolites identified. bkac057

  • The same year produced the first systematic structure-activity relationship study of α-PHP analogs at the DATsupported

    SAR study of 4-substituted α-PHP analogues; all behaved as 28- to >300-fold selective DAT vs SERT reuptake inhibitors. acschemneuro.3c00156

comparative-pharmacology6 · 5 ok
  • Extension of the α-alkyl chain from C1 to C4 progressively enhances DAT and NET inhibition potencysupported

    Extension of alkyl chain enhances NET/DAT inhibition potency. ijms22158277

  • In ICSS assays, α-PHP at 1.0 and 3.2 mg/kg i.p. facilitated responding comparably to cocaine at 10 mg/kg, suggesting at minimum equivalent reward-related potency on a per-milligram basissupported

    Doses of 1.0 and 3.2 mg/kg α-PHP facilitated ICSS responding similar to cocaine (10 mg/kg). j.etdah.2021.100004

  • Claim in comparative-pharmacology — not_supportednot supportedworking →

  • Mechanism: Both are pure DAT/NET reuptake inhibitors with no SERT activity or monoamine-releasing propertiessupported

    Pyrovalerone and MDPV classified as highly potent, selective DA and NA transporter inhibitors that do not evoke monoamine release (unlike amphetamines). j.1476-5381.2012.02145.x

  • Abuse liability: Equivalent in ICSS and locomotor stimulation assays in rodentssupported

    Abuse liability equivalent across all three α-pyrrolidino-phenone cathinones. j.drugalcdep.2021.108910

  • Duration: α-PHP's 37-hour serum half-life substantially exceeds α-PVP's reported elimination kinetics, suggesting a more prolonged effect profilesupported

    Serum elimination half-life 37 h. bkx080

chemistry4 · 2 ok
  • This series relationship is pharmacologically significant: extension of the α-alkyl chain enhances both DAT and NET inhibition potency within the pyrovalerone cathinone class.supported

    Extension of alkyl chain enhances NET/DAT inhibition potency. ijms22158277

  • Claim in chemistry — not_supportednot supportedworking →

  • Claim in chemistry — inconclusiveinconclusiveworking →

  • A systematic SAR study of 4-substituted α-PHP analogs demonstrated that most ring substitutions (4-F, 4-Cl, 4-Br, 4-CH₃, 4-OCH₃) maintain DAT inhibition potency within a narrow range (less than 3-fold variation), with 28- to greater than 300-fold selectivity for DAT over SERTsupported

    SAR study of 4-substituted α-PHP analogues; all behaved as 28- to >300-fold selective DAT vs SERT reuptake inhibitors. acschemneuro.3c00156

clinical-evidence4 · 4 ok
  • Grapp and colleagues reported a 29-case forensic toxicology series with confirmed α-PHP detectionsupported

    29-case series with analytically confirmed α-PHP. bkac057

  • The Fujita 2018 case report remains the only published human PK datasupported

    Human toxicokinetics case report: 39-year-old male presented with hallucinations and delusion. Serum α-PHP 175 ng/mL on arrival. Two-compartment model; serum elimination half-life 37 h. bkx080

  • The Swedish STRIDA project included α-PHP among 11 pyrovalerone-type NPS monitored over a 5-year surveillance period, documenting intoxication patterns within the broader pyrovalerone cathinone class.supported

    5-year STRIDA project data on 11 stimulant pyrovalerone NPS derivatives including α-PHP. 15563650.2017.1370097

  • Adamowicz reported a fetal death associated with maternal use of MDPHP and α-PHP — the first published case linking pyrrolidinohexanophenone cathinones to fetal mortalitysupported

    Case report of fetal death associated with use of MDPHP and α-PHP. First report of such outcome linking these synthetic cathinones to fetal mortality. 15563650.2018.1502443

neuroscience4 · 2 ok
  • Preclinical ICSS data directly demonstrate reward pathway engagement: α-PHP at 1.0 and 3.2 mg/kg i.p. decreased brain reward thresholds in a dose-dependent manner, comparable to cocaine at 10 mg/kgsupported

    Doses of 1.0 and 3.2 mg/kg α-PHP facilitated ICSS responding similar to cocaine (10 mg/kg). Rapid onset, long duration. j.etdah.2021.100004

  • Claim in neuroscience — not_supportednot supportedworking →

  • In vitro neurotoxicity data provide evidence of direct cellular damage: exposure of murine neural stem/progenitor cells (NSPCs) to α-PHP at concentrations of 25–2000 μM produced dose-dependent decreases in viability, proliferation, and clonal capability; resting membrane potential depolarization; and activation of apoptotic, autophagic, and necroptotic cell death pathways, with ultrastructural alterations visible by transmission electron microscopysupported

    α-PHP induced dose-dependent decrease in viability, proliferation, and clonal capability of murine NSPCs at 25–2000 μM. Apoptotic/autophagic/necroptotic pathway activation observed. Resting membrane potential depolarization. Ultrastructural alterations. biology12091225

  • Claim in neuroscience — inconclusiveinconclusiveworking →

pharmacokinetic-detail4 · 3 ok
  • Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →

  • The involvement of CYP1A2 and CYP2C19 as principal metabolizing enzymes has implications for drug-drug interactions: potent inhibitors of these enzymes (e.g., fluvoxamine for CYP1A2; omeprazole, fluconazole for CYP2C19) could theoretically slow α-PHP metabolism and prolong its already extended half-lifesupported

    For α-PHP: CYP1A2, CYP2C9, CYP2C19 mainly involved. dta.2355

  • The most comprehensive urinary metabolite profiling identified 11 phase I and 5 phase II metabolites in authentic human urine specimens. Dihydroxy-pyrrolidinyl-α-PHP was the most abundant urinary metabolite and is proposed as the optimal biomarker for confirmed α-PHP exposuresupported

    11 phase I + 5 phase II glucuronide metabolites identified. Main markers: dihydroxy-pyrrolidinyl-α-PHP and dihydro-α-PHP. bkac057

  • Hepatocyte incubation studies provided concordant results, confirming the dihydroxy-pyrrolidinyl metabolite as major and identifying additional products including α-PHP hexanol and 2'-keto-pyrrolidinyl variants.supported

    Identified α-PHP dihydroxy-pyrrolidinyl, hexanol, 2'-keto-pyrrolidinyl-hexanol, and 2'-keto-pyrrolidinyl as markers of use. Identified novel major metabolite α-PHP dihydroxy-pyrrolidinyl. ijms22010230

receptor-pharmacology4 · 2 ok
  • Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

  • The available evidence is qualitative: Davies and colleagues state that "using a synaptosomal assay, we previously reported that α-PHP is at least as potent as α-PVP as a dopamine transporter (DAT) reuptake inhibitor"supported

    Using a synaptosomal assay, α-PHP is at least as potent as α-PVP as a DAT reuptake inhibitor. acschemneuro.3c00156

  • For context, the class range for second-generation pyrovalerone cathinones (including α-PVP, MDPV, and structural analogs) spans:supported

    All pyrovalerone cathinones: DAT IC50=0.02–8.7 μM, NET IC50=0.03–4.6 μM. ijms22158277

  • Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

3Sources

24 consumed · sorted by year · feeds = sections resting on it

Sources
yearsourcetierstatusfeeds
2025α-PHP: Acute effects and pharmacokinetic in male and female mice, and clinical data on related intoxicationsBassi M, Roda E, Tirri M, Corli G, Bilel S, et al. · Drug and Alcohol Dependencedoi:10.1016/j.drugalcdep.2025.112596moderateconsumed4 sections
2024α-Pyrrolidinohexanophenone (α-PHP) and α-Pyrrolidinoisohexanophenone (α-PiHP): A ReviewDinis P, Franco J, Margalho C · Lifedoi:10.3390/life14040429moderateconsumed3 sections
2023Structure-Activity Relationships for a Recently Controlled Synthetic Cathinone Dopamine Transporter Reuptake Inhibitor: α-Pyrrolidinohexiophenone (α-PHP)Davies RA, Nguyen VT, Eltit JM, Glennon RA · ACS Chemical Neurosciencedoi:10.1021/acschemneuro.3c00156strongconsumed5 sections
2023The Designer Drug αPHP Affected Cell Proliferation and Triggered Deathly Mechanisms in Murine Neural Stem/Progenitor CellsRoda E, De Luca F, Priori EC, Ratto D, Pinelli S, et al. · Biologydoi:10.3390/biology12091225strongconsumed3 sections
2023Toxicological Investigation of a Case Series Involving the Synthetic Cathinone α-Pyrrolidinohexiophenone (α-PHP) and Identification of Phase I and II Metabolites in Human UrineGrapp M, Kaufmann C, Schwelm HM, Neukamm MA · Journal of Analytical Toxicologydoi:10.1093/jat/bkac057moderateconsumed6 sections
2022A review of synthetic cathinones emerging in recent years (2019–2022).Kuropka P, Zawadzki M, Szpot P · Forensic Toxicologydoi:10.1007/s11419-022-00639-5moderateconsumed1 section
2021A Strategy to Prioritize Emerging Drugs of Abuse for Analysis: Abuse Liability Testing Using Intracranial Self-Stimulation (ICSS) in Rats and Validation with α-Pyrrolidinohexanophenone (α-PHP)Baird TR, Davies RA, Glennon RA, Peace MR, Negus SS · Emerging Trends in Drugs, Addictions, and Healthdoi:10.1016/j.etdah.2021.100004strongconsumed4 sections
2021Effects of α-pyrrolidino-phenone cathinone stimulants on locomotor behavior in female rats.Taffe MA, Nguyen JD, Vandewater SA, Grant Y, Dickerson TJ · Drug and Alcohol Dependencedoi:10.1016/j.drugalcdep.2021.108910moderateconsumed3 sections
2021Evaluation of Cytotoxic and Mutagenic Effects of the Synthetic Cathinones Mexedrone, α-PVP and α-PHPLenzi M, Cocchi V, Gasperini S, Arfè R, Marti M, Hrelia P · International Journal of Molecular Sciencesdoi:10.3390/ijms22126320strongconsumed2 sections
2021Schedules of Controlled Substances: Placement of alpha-Pyrrolidinohexanophenone in Schedule I (Federal Register 2021-15114)US DEAurl:4f8faaee1f045d9fweakconsumedcited only
2021The Pharmacological Profile of Second Generation Pyrovalerone Cathinones and Related Cathinone Derivative.Kolaczynska KE, Thomann J, Hoener MC, Liechti ME · International journal of molecular sciencesdoi:10.3390/ijms22158277moderateconsumed5 sections
2020Designer drugs: mechanism of action and adverse effectsLuethi D, Liechti ME · Archives of Toxicologydoi:10.1007/s00204-020-02693-7strongconsumed1 section
2020Pyrrolidinyl Synthetic Cathinones α-PHP and 4F-α-PVP Metabolite Profiling Using Human Hepatocyte IncubationsCarlier J, Diao X, Giorgetti R, Busardò FP, Huestis MA · International Journal of Molecular Sciencesdoi:10.3390/ijms22010230strongconsumed2 sections
2020Substance Details: alpha-PHP (UNODC Laboratory and Scientific Section)UNODCurl:c64c4b4d0365fad5weakconsumedcited only
2019Alpha-PHP - Expert Committee on Drug Dependence Information RepositoryWHO ECDDurl:b9d2040a331315c9weakconsumedcited only
2019Fetal death associated with the use of 3,4-MDPHP and α-PHPAdamowicz P, Hydzik P · Clinical Toxicologydoi:10.1080/15563650.2018.1502443weakconsumed3 sections
2018Different in vitro and in vivo tools for elucidating the human metabolism of alpha-cathinone-derived drugs of abuseManier SK, Richter LHJ, Schäper J, Maurer HH, Meyer MR · Drug Testing and Analysisdoi:10.1002/dta.2355strongconsumed4 sections
2018Intoxications in the STRIDA project involving a panorama of psychostimulant pyrovalerone derivatives, MDPV copycatsBeck O, Bäckberg M, Signell P, Helander A · Clinical Toxicologydoi:10.1080/15563650.2017.1370097moderateconsumed1 section
2018Toxicokinetics of the Synthetic Cathinone α-PyrrolidinohexanophenoneFujita Y, Mita T, Usui K, Kamijo Y, Kikuchi S, Onodera M, Fujino Y, Inoue Y · Journal of Analytical Toxicologydoi:10.1093/jat/bkx080weakconsumed7 sections
2015Novel psychoactive substances (designer drugs): overview and pharmacology of modulators of monoamine signalingLiechti ME · Swiss Medical Weeklydoi:10.4414/smw.2015.14043moderateconsumed1 section
2014Bath salts, spice, and related designer drugs: the science behind the headlinesBaumann MH, Solis E, Watterson LR, Marusich JA, Fantegrossi WE, Wiley JL · Journal of Neurosciencedoi:10.1523/jneurosci.3223-14.2014moderateconsumedcited only
2012Pharmacological characterization of designer cathinones in vitroSimmler LD, Buser TA, Donzelli M, et al. · British Journal of Pharmacologydoi:10.1111/j.1476-5381.2012.02145.xmoderateconsumed5 sections
2012Psychoactive 'bath salts' intoxication with methylenedioxypyrovaleroneRoss EA, Reisfield GM, Watson MC, Chronister CW, Goldberger BA · The American Journal of Medicinedoi:10.1016/j.amjmed.2012.02.019moderateconsumed1 section
2011Acute poisoning involving the pyrrolidinophenone-type designer drug 4'-methyl-alpha-pyrrolidinohexanophenone (MPHP)Sauer C, Hoffmann K, Schimmel U, Peters FT · Forensic Science Internationaldoi:10.1016/j.forsciint.2011.02.026weakconsumed1 section
—Searched ClinicalTrials.gov for "alpha-PHP pyrrolidinohexanophenone" — no resultsabsenceno results—
—Searched Multiple sources for "alpha-PHP IC50 DAT dopamine transporter specific binding affinity" — no resultsabsenceno results—
—Searched PubMed for "tramadol stimulant cathinone interaction fatal toxicity" — no resultsabsenceno results—

4Docket

one filing per activity — decisions, correspondence, reports

  1. 0012026-04-28revisionRevision 1

    Initial LLM generation (v5 pipeline, wiki)

    psx:substance/a-php/version/1
  2. 0022026-06-04proposal55 value proposals approved together

    one review action inferred from a shared reviewer and instant — the graph records one activity per proposal

    55 items in this filing

    • dose_tier · light
    • dose_tier · common
    • dose_tier · strong
    • dose_tier · heavy
    • timeline · oral · onset
    • timeline · oral · come_up
    • timeline · oral · peak
    • timeline · oral · plateau
    • timeline · oral · resolution
    • timeline · oral · afterglow
    • timeline · insufflated · onset
    • timeline · insufflated · come_up
    • timeline · insufflated · peak
    • timeline · insufflated · plateau
    • timeline · insufflated · resolution
    • timeline · insufflated · afterglow
    • timeline · smoked · onset
    • timeline · smoked · come_up
    • timeline · smoked · peak
    • timeline · smoked · plateau
    • timeline · smoked · resolution
    • timeline · smoked · afterglow
    • toxicity
    • dependence · full
    • withdrawal
    • tolerance
    • dosage · oral
    • dosage · insufflated
    • dosage · smoked
    • duration · oral · onset
    • duration · oral · come_up
    • duration · oral · peak
    • duration · oral · offset
    • duration · oral · total
    • duration · oral · aftereffects
    • duration · insufflated · onset
    • duration · insufflated · come_up
    • duration · insufflated · peak
    • duration · insufflated · offset
    • duration · insufflated · total
    • duration · insufflated · aftereffects
    • duration · smoked · onset
    • duration · smoked · come_up
    • duration · smoked · peak
    • duration · smoked · offset
    • duration · smoked · total
    • duration · smoked · aftereffects
    • contraindication · cardiovascular
    • contraindication · psychiatric
    • contraindication · psychiatric
    • contraindication · pregnancy_breastfeeding
    • contraindication · neurological
    • contraindication · other
    • contraindication · other
    psx:substance/a-php/proposal/dose_tier/69ce161b-495e-4368-8286-4f0ff4797257
  3. 0032026-06-04publicationPublication — backfill

5Issued documents

what the notice, info card and emergency page said, by hash

Issued documents
documentcontent hashissuedfrom versionsuperseded
info_card1ab5b2ca1b17ca15ed827d25…2026-10-19 20:30Revision 1current
emergency58d3299a8754d788e3d74c0e…2026-09-04 04:28Revision 1current
info_card87f16cac9a5a25bc4eb110b4…2026-09-04 04:28Revision 1superseded2026-10-19
notice1813f6d43358bb1394dd8c16…2026-09-04 04:28Revision 1current