generation run 2026-05-07
103 min completedmodel pipeline-v5plan not recordedrun/a80f8b0d…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
- structural_inference
- safety_data_unverified
Reproduce
- inputs
- 28 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
22 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | 3-chloro-PCP phencyclidine analog pharmacology | 15 | 1 | Only paper directly studying 3-Cl-PCP in vivo |
| 2 | PubMed | phencyclidine NMDA receptor antagonist sigma receptor binding pharmacology review | 3 | 3 | — |
| 3 | PubMed | 3-MeO-PCP methoxyphencyclidine case report intoxication forensic toxicology | 5 | 5 | — |
| 4 | PubMed · absence | 3-Cl-PCP arylcyclohexylamine dissociative binding affinity NMDA | 0 | — | — |
| 5 | Crossref | 10.1124/jpet.123.001942 | 1 | 1 | — |
| 6 | PubChem | 1-(1-(3-chlorophenyl)cyclohexyl)piperidine | 1 | 1 | Confirmed chemical identity |
| 7 | ClinicalTrials.gov · absence | 3-chloro phencyclidine dissociative arylcyclohexylamine | 0 | — | — |
| 8 | PubMed · absence | phencyclidine ring-substituted analogs structure activity relationship CNS | 0 | — | — |
| 9 | PubChem · absence | 3-Cl-PCP | 0 | — | — |
| 10 | OpenAlex · absence | 3-chlorophencyclidine arylcyclohexylamine NMDA receptor | 0 | — | — |
| 11 | PubMed | PMID 10063482 - Jentsch & Roth 1999 PCP neuropsychopharmacology | 1 | 1 | — |
| 12 | Federal Register · absence | 3-Cl-PCP scheduling DEA | 0 | — | — |
| 13 | PubMed | PMID 12232776 - Kapur & Seeman 2002 PCP at D2 and 5-HT2 receptors | 1 | 1 | — |
| 14 | UNODC | — | 1 | — | — |
| 15 | WebSearch | 3-Cl-PCP pharmacology NMDA binding affinity dissociative | 10 | 1 | — |
| 16 | WebSearch | 3-Cl-PCP first synthesized 2020 market research chemical history | 10 | 1 | — |
| 17 | WebSearch | 3-Cl-PCP DEA analog act scheduling 2024 | 10 | — | — |
| 18 | OpenAlex | Shaw Fantegrossi arylcyclohexylamine PCP analog rodent 2024 | 1 | — | — |
| 19 | WebSearch | 3-Cl-PCP legal status UK Psychoactive Substances Act scheduling | 10 | — | — |
| 20 | PubMed/PMC | PMID 20440387 - Bey & Patel 2007 PCP intoxication review | 1 | — | — |
| 21 | PubMed | PMID 27314670 - Wallach 2016 diphenidine pharmacology 46 receptors | 1 | — | — |
| 22 | WebSearch | phencyclidine PCP human pharmacokinetics plasma half-life alkaline urine | 10 | — | — |
73 claims by section — every cited sentence, checked against its source
safety24 · 18 ok
Claim in safety — inconclusiveinconclusiveworking →
For comparison, in silico toxicity modeling for related PCP analogs (3-HO-PCP, 3-MeO-PCP, 4-MeO-PCP) estimates oral LD₅₀ in rats at approximately 200–630 mg/kg and intravenous LD₅₀ in mice at approximately 25–59 mg/kgsupported
In silico toxicity profiling of PCP analogues: rat oral LD50 200-630 mg/kg range, IV LD50 in mice ~25-59 mg/kg. s00204-025-04242-6
Claim in safety — inconclusiveinconclusiveworking →
PCP-class NMDA antagonists produce sympathomimetic cardiovascular effects — tachycardia and hypertension — via catecholamine reuptake inhibition. In silico modeling for PCP analogs predicts hERG channel inhibition (IC₅₀ ~4.9–12.3 µM), suggesting risk of QT interval prolongation and cardiac arrhythmia.partially supported
Cardiotoxicity signals (hERG inhibition). Lung, liver, blood as organ targets. s00204-025-04242-6
Rhabdomyolysis and acute kidney injury have been documented for 3-methyl-PCP, a closely related ring-substituted PCP analogsupported
Rhabdomyolysis and acute kidney injury reported. s13181-026-01122-y
Claim in safety — inconclusiveinconclusiveworking →
PCP undergoes hepatic bioactivation to reactive intermediates (quinone methide) via CYP2B6, a pathway that could generate hepatotoxic metabolitessupported
PCP undergoes bioactivation via CYP2B6 and CYP2C19 in human liver microsomes. Two pathways identified: dihydropyridinium formation and quinone methide intermediate from para-hydroxylation. GSH conjugates detected. pmid:17892269
Claim in safety — inconclusiveinconclusiveworking →
PCP is among the most potent pharmacological psychotomimetics, producing schizophrenia-like positive symptoms (hallucinations, delusions), negative symptoms (social withdrawal, flattened affect), and cognitive deficits (working memory impairment, disorganized thought). 3-Cl-PCP produced dose-dependent psychosis-like neurocognitive deficits in a rat model specifically designed for validity against the human psychosis construct.supported
Administration of noncompetitive NMDA/glutamate receptor antagonists, such as phencyclidine (PCP) and ketamine, to humans induces a broad range of schizophrenic-like symptomatology. s0893-133x(98)00060-8
PCP is among the most potent pharmacological psychotomimetics, producing schizophrenia-like positive symptoms (hallucinations, delusions), negative symptoms (social withdrawal, flattened affect), and cognitive deficits (working memory impairment, disorganized thought). 3-Cl-PCP produced dose-dependent psychosis-like neurocognitive deficits in a rat model specifically designed for validity against the human psychosis construct.supported
PCP and 3-Cl-PCP both elicited dose-dependent psychosis-like neurocognitive deficits not observed with cocaine or morphine. jpet.123.001942
Prolonged psychiatric sequelae are documented for the closely related compound 3-MeO-PCP, with hallucinations persisting up to six weeks after a single exposuresupported
Hallucinations lasted 6 weeks. j.jflm.2014.04.007
A case report documents attempted murder in a patient under the combined influence of 3-MeO-PCP and MDPVsupported
3-MeO-PCP + MDPV + butane inhalation induced vivid hallucinations and bizarre delusions leading to violent behavior (attempted murder). j.jflm.2014.04.007
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
In squirrel monkeys, approximately 2-fold tolerance developed after 82–126 days of chronic dosing.supported
Chronic PCP administration (82-126 days) in squirrel monkeys demonstrated approximately 2-fold tolerance shift in dose-response curves. pmid:412949
Cross-tolerance is documented between PCP and sigma agonists (SKF-10047) and is expected across the dissociative class, including ketamine, dextromethorphan, methoxetamine, and other NMDA antagonists.supported
Cross-tolerance demonstrated between PCP and sigma agonist SKF-10047. pmid:6317323
Physical dependence has been demonstrated for PCP in rats after 7 days of continuous intravenous infusion; the withdrawal syndrome included piloerection, audiogenic seizures, weight loss, and reduced locomotor activity, emerging approximately 4 hours after cessation and resolving mostly within 24 hours.supported
PCP infusion in rats induced tolerance within 3.5 days and physical dependence within 7 days. Abstinence syndrome included piloerection, audiogenic seizures, weight loss, reduced locomotor activity. First withdrawal signs 4hr post-cessation. pmid:4040569
Reinforcing properties: PCP reliably maintains self-administration in animal models, confirming genuine addictive potentialsupported
PCP analogs can function as reinforcers for self-administration. pmid:2899317
Polydrug use was identified in 53% of ketamine-related fatalities in a systematic review of dissociative overdose deaths, establishing this as the highest-risk interaction category for the class.supported
Polydrug use in 53% of cases. 00952990.2022.2132506
CYP2B6 interactions: 3-Cl-PCP is expected to be metabolized primarily by CYP2B6, with secondary metabolism via CYP3A4 and CYP2C19partially supported
PCP undergoes bioactivation via CYP2B6 and CYP2C19 in human liver microsomes. pmid:17892269
CYP2B6 interactions: 3-Cl-PCP is expected to be metabolized primarily by CYP2B6, with secondary metabolism via CYP3A4 and CYP2C19partially supported
Ketamine metabolized by CYP3A4 and CYP2B6 (N-demethylation to norketamine). 20961790.2017.1285219
Pre-existing psychotic disorders: NMDA receptor antagonists are established psychotomimetics that exacerbate schizophrenia spectrum symptoms. 3-Cl-PCP is contraindicated in individuals with schizophrenia, schizoaffective disorder, or a personal or family history of psychosis.supported
Administration of noncompetitive NMDA/glutamate receptor antagonists, such as phencyclidine (PCP) and ketamine, to humans induces a broad range of schizophrenic-like symptomatology. s0893-133x(98)00060-8
Cardiovascular disease: Sympathomimetic effects (tachycardia, hypertension) and predicted hERG channel inhibition represent serious risk for individuals with pre-existing cardiac conditions, conduction abnormalities, or hypertension.supported
Cardiotoxicity signals (hERG inhibition). s00204-025-04242-6
Polydrug involvement accounts for the majority of dissociative-related deaths.supported
Polydrug use in 53% of cases. Mostly male. Ages 2-65 years. Ketamine preponderant in fatalities. 00952990.2022.2132506
pharmacology16 · 9 ok
3-Cl-PCP is presumed to exert its primary effects through non-competitive, use-dependent antagonism of the NMDA receptor (N-methyl-D-aspartate receptor), binding within the open ion channel at the phencyclidine binding sitesupported
Administration of noncompetitive NMDA/glutamate receptor antagonists, such as phencyclidine (PCP) and ketamine, to humans induces a broad range of schizophrenic-like symptomatology. s0893-133x(98)00060-8
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Secondary pharmacological activity is expected at sigma-1 and sigma-2 receptors, where the sigma/PCP site partially overlaps with the NMDA-associated binding site; sigma ligands at these sites modulate both glutamatergic and dopaminergic neurotransmission. Monoamine reuptake inhibition — affecting dopamine, norepinephrine, and serotonin transporters — contributes the stimulant component characteristic of PCP-class compounds.supported
Sigma receptors regulate glutamatergic system via NMDA receptor modulation, which in turn interferes with dopaminergic neurotransmission. pmid:8632719
No substance-specific binding affinity data exist for 3-Cl-PCP at any receptor target. The pharmacological class designation (NMDA antagonist, sigma agonist, dopamine receptor ligand) derives from: (1) structural analogy with PCP, from which 3-Cl-PCP differs only by a chlorine atom at the meta position of the phenyl ring; (2) in vivo behavioral pharmacology demonstrating a PCP-like profile in rodents; and (3) class-level receptor binding data from the parent compound.supported
Assessed locomotor effects of PCP and its 3-OH, 3-MeO, 3-Cl, and 4-MeO analogs in mice. Used drug discrimination in rats to assess PCP-like interoceptive effects. jpet.123.001942
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Pistis (2024) provided expert commentary contextualizing these findings within the evolving new psychoactive substance challenge for novel dissociative analogs.supported
Editorial/commentary accompanying Shaw et al. 2024 in JPET, discussing the evolving NPS landscape for novel dissociative anesthetic analogs. jpet.124.002109
PCP demonstrates a volume of distribution of 6.2 L/kg, reflecting extensive tissue distribution driven by high lipophilicitysupported
Volume of distribution 6.2 L/kg. pmid:6852275
Plasma elimination half-life averages 17.6 hours across 16 subjects, with a range extending beyond 2 days in some individualssupported
Weighted mean terminal half-life 17.6h (n=16, range up to 2+ days). pmid:6852275
Claim in pharmacology — inconclusiveinconclusiveworking →
Hepatic metabolism accounts for approximately 90% of PCP clearance, proceeding via oxidative hydroxylation catalyzed primarily by CYP2B6, with CYP2C19 and CYP3A4 as secondary pathwayspartially supported
PCP undergoes bioactivation via CYP2B6 and CYP2C19 in human liver microsomes. pmid:17892269
Claim in pharmacology — inconclusiveinconclusiveworking →
Only approximately 9% of the parent compound is excreted unchanged in urine; renal excretion is pH-dependent, with acidification increasing clearance and alkalinization reducing itpartially supported
Renal clearance of PCP is pH-dependent; alkaline urine reduces excretion, acidic urine increases it. pmid:7128004
Claim in pharmacology — inconclusiveinconclusiveworking →
For 3-Cl-PCP specifically, the chlorine substituent at position 3 of the phenyl ring is expected to alter metabolic patterns. In silico ADME modeling for methoxy-substituted PCP analogs demonstrated CYP3A4, CYP2D6, and CYP2C19 as primary metabolizing enzymessupported
CYP3A4, CYP2D6, CYP2C19 metabolic liability. O-demethylation as primary metabolic pathway. s00204-025-04283-x
summary7 · 6 ok
Duration is expected to be prolonged, consistent with the high lipophilicity and extensive tissue redistribution characteristic of PCP-class compounds.supported
pharmacokinetics (Vd 6.2 L/kg, half-life 17.6h, 90% hepatic metabolism) pmid:20440387
A single peer-reviewed primary study exists: Shaw et al. (2024) characterized 3-Cl-PCP's behavioral pharmacology in rodents, demonstrating PCP-like locomotor stimulation, full substitution for PCP in drug discrimination assays, and dose-dependent psychosis-like neurocognitive deficitssupported
All novel ACXs substituted partially or fully for PCP. PCP and 3-Cl-PCP both elicited dose-dependent psychosis-like neurocognitive deficits not observed with cocaine or morphine. jpet.123.001942
As an arylcyclohexylamine, 3-Cl-PCP is presumed to act primarily through non-competitive antagonism of the NMDA receptor at the intrachannel phencyclidine binding site, with secondary activity at sigma receptors and monoamine transporterssupported
Administration of noncompetitive NMDA/glutamate receptor antagonists, such as phencyclidine (PCP) and ketamine, to humans induces a broad range of schizophrenic-like symptomatology. Comprehensive review of PCP pharmacology, NMDA hypofunction hypothesis, dopaminergic effects. s0893-133x(98)00060-8
The behavioral profile in rodents — stimulation, dissociative interoceptive cues, and cognitive disruption — is consistent with this mechanismsupported
Assessed locomotor effects of PCP and its 3-OH, 3-MeO, 3-Cl, and 4-MeO analogs in mice. Used drug discrimination in rats to assess PCP-like interoceptive effects. 3-Cl-PCP specifically studied for psychosis-like neurocognitive deficits. jpet.123.001942
Claim in summary — inconclusiveinconclusiveworking →
Dependence liability is rated moderate for both physical and psychological dimensions, based on PCP class datasupported
PCP infusion in rats induced tolerance within 3.5 days and physical dependence within 7 days. pmid:4040569
NMDA receptor antagonists are established psychotomimetics; 3-Cl-PCP produced psychosis-like cognitive deficits in the only published behavioral studysupported
PCP and 3-Cl-PCP both elicited dose-dependent psychosis-like neurocognitive deficits not observed with cocaine or morphine. jpet.123.001942
comparative-pharmacology6 · 4 ok
Clinical case reports document both non-fatal intoxications and fatalities, and the DEA permanently placed it in Schedule I effective April 2026partially supported
Reports non-fatal intoxication and seven deaths involving 3-MeO-PCP in Sweden 2014-2016. j.forsciint.2017.02.034
Direct head-to-head binding data are not available for 3-Cl-PCP, but behavioral pharmacology data from Shaw et al. (2024) provide a framework for comparison.supported
Assessed locomotor effects of PCP and its 3-OH, 3-MeO, 3-Cl, and 4-MeO analogs in mice. Used drug discrimination in rats. jpet.123.001942
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Case reports document prolonged psychiatric sequelae including hallucinations persisting up to six weekssupported
Hallucinations lasted 6 weeks. j.jflm.2014.04.007
Ketamine's plasma half-life of 2–3 hours is an order of magnitude shorter than PCP's 17.6 hours, and 3-Cl-PCP's duration is expected to align more closely with PCP than with ketamine based on shared structural features (intact piperidine ring, absence of carbonyl)supported
Weighted mean terminal half-life 17.6h (n=16, range up to 2+ days). pmid:6852275
neuroscience6 · 3 ok
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Mesolimbic dopamine activation: NMDA antagonism in the ventral tegmental area, combined with direct monoamine reuptake inhibition, produces secondary dopaminergic activation in the nucleus accumbens — the neural substrate for the stimulant, euphoric, and reinforcing properties of PCP-class compounds.supported
Comprehensive review of PCP pharmacology, NMDA hypofunction hypothesis, dopaminergic effects. s0893-133x(98)00060-8
NMDA receptor hypofunction model of psychosis: PCP-induced psychosis provided the original pharmacological model of schizophrenia, and the NMDA hypofunction hypothesis remains one of the dominant theoretical frameworks in psychosis researchsupported
NMDA hypofunction hypothesis, dopaminergic effects. s0893-133x(98)00060-8
Shaw et al. (2024) demonstrated that 3-Cl-PCP produces the cognitive deficit component of this triad with specificity — cocaine and morphine did not impair rule-governed behavior in the same assay.supported
PCP and 3-Cl-PCP both elicited dose-dependent psychosis-like neurocognitive deficits not observed with cocaine or morphine. jpet.123.001942
Claim in neuroscience — inconclusiveinconclusiveworking →
pharmacokinetic-detail6 · 6 ok
The primary metabolic reactions include hydroxylation of the piperidine ring (producing a dihydropyridinium intermediate) and para-hydroxylation of the phenyl ring (producing a quinone methide intermediate)supported
Two pathways identified: dihydropyridinium formation and quinone methide intermediate from para-hydroxylation. pmid:17892269
CYP2B6 is the primary enzyme responsible for both bioactivation pathways, with CYP2C19 and CYP3A4 contributing as secondary enzymes.partially supported
PCP undergoes bioactivation via CYP2B6 and CYP2C19 in human liver microsomes and recombinant P450 2B enzymes. pmid:17892269
CYP2B6 is the primary enzyme responsible for both bioactivation pathways, with CYP2C19 and CYP3A4 contributing as secondary enzymes.partially supported
Ketamine metabolized by CYP3A4 and CYP2B6 (N-demethylation to norketamine). 20961790.2017.1285219
In silico ADME modeling for methoxy-substituted PCP analogs identified CYP3A4, CYP2D6, and CYP2C19 as primary metabolizing enzymes, with O-demethylation as the dominant metabolic stepsupported
CYP3A4, CYP2D6, CYP2C19 metabolic liability. O-demethylation as primary metabolic pathway. s00204-025-04283-x
Urine acidification increases the fraction of ionized drug in the renal tubule, reducing reabsorption and increasing clearancesupported
Renal clearance of PCP is pH-dependent; alkaline urine reduces excretion, acidic urine increases it. pmid:7128004
Modern clinical guidelines do not recommend urine acidification for PCP intoxication due to the risk of acute tubular necrosis.supported
management (benzodiazepines, activated charcoal, avoid urinary acidification). pmid:20440387
receptor-pharmacology4 · 4 ok
The PCP parent compound shows highest affinity for the NMDA channel site (Ki ≈ 2 µM), with substantially lower affinities at serotonergic (Ki ≈ 5 µM) and dopaminergic (Ki ≈ 37 µM) targetssupported
PCP has NMDA receptor affinity ~2 µM, 5-HT2 affinity ~5 µM, D2 affinity ~37 µM. pmid:12232776
PCP binds to sigma sites that partially overlap with the NMDA-associated PCP site, and sigma receptor activation modulates both glutamatergic and dopaminergic neurotransmissionsupported
Sigma receptors regulate glutamatergic system via NMDA receptor modulation, which in turn interferes with dopaminergic neurotransmission. pmid:8632719
PCP binds to sigma sites that partially overlap with the NMDA-associated PCP site, and sigma receptor activation modulates both glutamatergic and dopaminergic neurotransmissionsupported
Reviews sigma and PCP receptor binding sites; PCP receptor has preferential affinity for phencyclidine analogs and other non-competitive NMDA receptor antagonists. pmid:2172677
Shaw et al. (2024) demonstrated that 3-chloro substitution preserves PCP-like behavioral activity — full locomotor stimulation, PCP substitution in drug discrimination, and psychosis-like cognitive effects — suggesting that affinity at the primary NMDA target is not substantially diminished by this modificationsupported
Addition of Cl at 3-position did not reduce locomotor effectiveness. All novel ACXs substituted partially or fully for PCP. PCP and 3-Cl-PCP both elicited dose-dependent psychosis-like neurocognitive deficits. jpet.123.001942
history2 · 2 ok
Extensive structure-activity relationship work on ring-substituted PCP analogs was conducted through the 1960s to 1980s, establishing the arylcyclohexylamine scaffold as a prolific source of pharmacological diversity.supported
Reviews SAR of arylcyclohexylamine analogs of PCP at PCP-binding sites and drug discrimination. pmid:2899317
The methoxy-substituted analogs 3-MeO-PCP and 4-MeO-PCP appeared on the research chemical market around 2011, predating the chloro-substituted variants by approximately a decade. 3-Cl-PCP represents the first chlorine-at-meta-position PCP analog to achieve meaningful distribution as an NPS.partially supported
Drug appeared on illicit market in 2011. j.forsciint.2017.02.034
clinical-evidence1 · 1 ok
The only published primary research on 3-Cl-PCP is a preclinical rodent study examining behavioral pharmacology — locomotor activity, drug discrimination, and neurocognitive effects in mice and ratssupported
Assessed locomotor effects of PCP and its 3-OH, 3-MeO, 3-Cl, and 4-MeO analogs in mice. Used drug discrimination in rats to assess PCP-like interoceptive effects. 3-Cl-PCP specifically studied for psychosis-like neurocognitive deficits. jpet.123.001942
effects-overview1 · 1 ok
3-Cl-PCP is positioned pharmacologically closer to PCP than to ketamine or methoxetamine — the intact piperidine ring, absence of a carbonyl group, and PCP-equivalent behavioral profile in rodent drug discrimination all support this alignmentsupported
All novel ACXs substituted partially or fully for PCP. Addition of Cl at 3-position did not reduce locomotor effectiveness. jpet.123.001942