generation run 2026-04-26
44 min completedmodel pipeline-v5plan not recordedrun/c525191b…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- sparse_evidence
- class_inference_only
- clinical_data_limited
Reproduce
- inputs
- 21 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
15 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | ClinicalTrials.gov · absence | rolicyclidine PCPy dissociative | 0 | — | No trials to report |
| 2 | PubChem | rolicyclidine | 1 | 1 | Confirmed chemical identity, molecular formula, weight, InChIKey. SMILES not returned by API. |
| 3 | PubMed | rolicyclidine PCPy pharmacology | 5 | 5 | All directly relevant to rolicyclidine pharmacology, clinical toxicology, and behavioral effects |
| 4 | PubMed | phencyclidine metabolism cytochrome P450 CYP enzyme | 7 | 3 | PCP/PCPy alpha-oxidation paper directly reports on pyrrolidine analogue metabolism |
| 5 | PubMed | phencyclidine analogue NMDA receptor binding affinity arylcyclohexylamine | 2 | 2 | Provides SAR context and receptor binding data for PCP analogue class |
| 6 | OpenAlex | rolicyclidine PCPy 1-phenylcyclohexyl pyrrolidine | 4 | 2 | 3-MeO-PCPy metabolism paper directly relevant to rolicyclidine analog. Legal highs review provides context. |
| 7 | WebSearch | rolicyclidine PHP synthesis history Maddox 1965 | 10 | 2 | Historical synthesis record |
| 8 | PubMed | PCP analogue self-administration reinforcing behavioral drug dependence | 2 | 1 | Documents PCP analogue reinforcing properties and abuse potential mechanism via DAT/dopamine pathways |
| 9 | WebSearch | rolicyclidine PCPy legal status Schedule I DEA controlled substance US UK | 10 | 3 | Legal status data for major jurisdictions |
| 10 | NCATS Inxight Drugs | — | 1 | 3 | Verified SMILES and CAS number from authoritative federal database |
| 11 | PubMed | phencyclidine PCP self-administration reinforcing dependence monkey primate | 10 | 2 | PCP dependence and withdrawal data applicable to PCPy by pharmacological class |
| 12 | UNODC | — | 1 | 1 | Official UN international scheduling status |
| 13 | Multiple sources | Rolicyclidine data cross-reference | 23 | — | Final cross-reference confirms data integrity; key gap is absence of quantitative binding affinity data (Ki/EC50) for rolicyclidine specifically |
| 14 | WebSearch | rolicyclidine melting point solubility physical properties chemical | 10 | 4 | Physical property data for rolicyclidine not available in academic literature; commercial databases are the only source |
| 15 | PubMed · absence | phenylcyclohexylpyrrolidine PCPy PHP sigma NMDA binding radioligand displacement | 0 | — | Confirmed absence of specific binding affinity data for rolicyclidine - key gap documented |
64 claims by section — every cited sentence, checked against its source
safety14 · 12 ok
PCP-class drugs carry established risks of psychosis, cardiovascular stimulation, and respiratory depression at high doses; rolicyclidine-specific incidence data are absentsupported
Comprehensive review of designer drug mechanisms including dissociative NMDA receptor antagonists. Covers adverse effects and health risks. s00204-020-02693-7
No LD₅₀ or human lethal dose data have been published for rolicyclidine. Acute toxicity is inferred from PCP class pharmacology: cardiovascular stimulation (hypertension, tachycardia), respiratory depression at high doses, hyperthermia, and rhabdomyolysis are documented for PCP and are plausibly applicable to rolicyclidine.supported
Comprehensive review of designer drug mechanisms including dissociative NMDA receptor antagonists. Covers adverse effects and health risks. s00204-020-02693-7
Claim in safety — inconclusiveinconclusiveworking →
In a single case, physostigmine produced rapid symptom reversal, suggesting anticholinergic-like features in the acute toxidrome.supported
Treatment with physostigmine (IM) produced a rapid and sustained reversal of these symptoms. pmid:7175996
Rolicyclidine's mechanism-based inhibition of hepatic CYP enzymes introduces a toxicity dimension not shared by most recreational dissociativessupported
PCPY and PCP analogues cause mechanism-based CYP inhibition. pmid:2891481
PCP-class dissociatives are established precipitants of acute psychosis, characterized by hallucinations, paranoid ideation, agitation, and disorganized behaviorsupported
Twenty white males who presented with psychosis were later found to have ingested PHP. pmid:4057312
PCP-class dissociatives are established precipitants of acute psychosis, characterized by hallucinations, paranoid ideation, agitation, and disorganized behaviorsupported
Review of novel psychoactive substances (NPS) including dissociatives similar to ketamine and PCP. Covers pharmacodynamics, subjective/physical effects, harmfulness, and dependency risk for each class. 2045125314559539
PHP-induced psychosis is clinically indistinguishable from PCP psychosis in presentationsupported
Results of haloperidol treatment of PHP psychosis were similar to previously published reports with phencyclidine (PCP) psychosis. pmid:4057312
Violence and self-injury during PCP-class intoxication are recognized risks, driven by the combination of psychotomimesis, motor disinhibition, and analgesiasupported
Comprehensive review of designer drug mechanisms including dissociative NMDA receptor antagonists. Covers adverse effects and health risks. s00204-020-02693-7
Oral PCP self-administration in rhesus monkeys produces physical dependence with measurable withdrawal, and males show greater withdrawal severity than femalessupported
Males show greater PCP withdrawal severity than females in primates. PCP intake equal when weight normalized. pmid:16503706
PCP withdrawal reduces operant responding maintained by food reinforcement, indicating physiological disruption beyond psychological cravingsupported
Withdrawal of PCP reduces operant responding maintained by food, demonstrating dependence. s00213-009-1636-y
Claim in safety — not_supportednot supportedworking →
Cross-tolerance among PCP-class dissociatives is supported by full generalization in drug discrimination paradigms — consistent with shared NMDA open-channel blockade as the common mechanism driving both tolerance and cross-tolerancesupported
PHP and four other analogues generalized to PCP with dose-dependent responding. pmid:7208560
Rolicyclidine's mechanism-based CYP inhibition creates the most pharmacologically distinctive interaction risk among PCP analoguespartially supported
Relative rates of inactivation: PCP >= PCPY > PCHMI. pmid:2891481
pharmacology10 · 8 ok
Rolicyclidine is a non-competitive NMDA receptor antagonist that binds at the phencyclidine site within the ion channel pore of the NMDA receptor complexsupported
PCP-like drugs inhibit NMDA-stimulated ACh and DA release via PCP-sigma receptor. Allosteric link between PCP-sigma receptor and NMDA receptor suggested. pmid:2875174
Claim in pharmacology — inconclusiveinconclusiveworking →
Rolicyclidine is also classified as a sigma receptor agonist and dopamine reuptake inhibitor, consistent with the pharmacological profile of arylcyclohexylamines as a classpartially supported
Sigma binding sites have preferential affinity for benzomorphan opiates. PCP receptor has preferential affinity for PCP analogues and non-competitive NMDA antagonists. pmid:2172677
Among PCP analogues studied, rolicyclidine generates the largest proportion of PCA relative to PCP and other ring-size variants.supported
Pyrrolidine analogue generated largest proportion of PCA. pmid:2171233
Metabolic pathway data from the closely related compound 3-methoxyrolicyclidine (3-MeO-PCPy) identify multiple aliphatic hydroxylations at the cyclohexyl and pyrrolidine rings, a single aromatic hydroxylation, carboxylation following ring opening, and glucuronidation of hydroxylated metabolitessupported
multiple aliphatic hydroxylations at cyclohexyl and pyrrolidine rings, aromatic hydroxylation, carboxylation after ring opening, O-demethylation, glucuronidation. 1570159x14666161018151716
CYP2B6 catalyzes aliphatic hydroxylations, while CYP2C9 and CYP2D6 catalyze O-demethylation in the methoxylated analoguesupported
CYP2B6 for aliphatic hydroxylations; CYP2C9 and CYP2D6 for O-demethylation. 1570159x14666161018151716
CYP2B6 is likely the primary enzyme for aliphatic hydroxylation; CYP3A4 involvement is inferred from human liver microsome studies of the parent compound PCP.supported
CYP3A major role in PCP metabolism in human liver microsomes. pmid:9152594
Rolicyclidine causes mechanism-based (irreversible) inhibition of cytochrome P450 enzymessupported
PCPY and PCP analogues cause mechanism-based CYP inhibition. pmid:2891481
Claim in pharmacology — inconclusiveinconclusiveworking →
The mechanism requires a substituted nitrogen within a heterocyclic ring; the cyclic carbinolamine intermediate formed during alpha-carbon oxidation is implicated as the species responsible for enzyme inactivation.partially supported
requires substituted nitrogen in heterocyclic ring. pmid:2891481
summary8 · 7 ok
In behavioral pharmacology, rolicyclidine occupies an intermediate position among PCP analogues — more potent than ketamine and the morpholine analogue (PCM) but less potent than PCP and eticyclidine (PCE) in both discriminative stimulus and operant suppression assayspartially supported
Relative potency for drug-lever responding: TCP > PCP = PCE > PHP > PCM > ketamine. pmid:7208560
Claim in summary — inconclusiveinconclusiveworking →
Its current significance is limited to structure-activity relationship studies of the arylcyclohexylamine series and its documented role as a substrate in cytochrome P450 mechanism-based inhibition research.supported
PCPY and PCP analogues cause mechanism-based CYP inhibition. pmid:2891481
As an arylcyclohexylamine, rolicyclidine is presumed to act through use-dependent blockade of the NMDA receptor ion channel pore, with secondary activity at sigma receptors and the dopamine transporter inferred from class pharmacologysupported
PCP receptor has preferential affinity for PCP analogues and non-competitive NMDA antagonists. Physiological significance associated with blockade of NMDA receptor. pmid:2172677
Clinical case reports describe a psychotomimetic syndrome indistinguishable from PCP intoxication — hallucinations, agitation, disorganized thinking, and motor impairment — with presentation and treatment response closely paralleling PCP psychosissupported
A case is presented of a 31-year-old male who showed neurological and psychic symptoms following ingestion of phenylcyclohexylpyrrolidine (PHP). pmid:7175996
Clinical case reports describe a psychotomimetic syndrome indistinguishable from PCP intoxication — hallucinations, agitation, disorganized thinking, and motor impairment — with presentation and treatment response closely paralleling PCP psychosissupported
Results of haloperidol treatment of PHP psychosis were similar to previously published reports with phencyclidine (PCP) psychosis. pmid:4057312
No controlled toxicity data exist for rolicyclidine — no LD₅₀, therapeutic index, or human lethal dose has been published. The compound is a documented mechanism-based inhibitor of hepatic cytochrome P450 enzymes, creating pharmacokinetic drug-drug interaction risk atypical among recreational dissociativessupported
PCPY and PCP analogues cause mechanism-based CYP inhibition. NADPH-dependent; requires substituted nitrogen in heterocyclic ring. pmid:2891481
Dependence liability is inferred from PCP-class primate studies demonstrating physical dependence and reinforcing propertiessupported
Males show greater PCP withdrawal severity than females in primates. pmid:16503706
pharmacokinetic-detail6 · 5 ok
Primary metabolism proceeds through CYP2B6-catalyzed aliphatic hydroxylation, based on data from the closely related 3-methoxyrolicyclidinesupported
CYP2B6 for aliphatic hydroxylations. 1570159x14666161018151716
CYP3A4 involvement is inferred from PCP metabolism in human liver microsomessupported
CYP3A major role in PCP metabolism in human liver microsomes. pmid:9152594
Rolicyclidine is itself a mechanism-based CYP inhibitor, which may prolong its own elimination and that of co-administered drugs in a dose-dependent manner.supported
PCPY and PCP analogues cause mechanism-based CYP inhibition. NADPH-dependent. pmid:2891481
The mechanism-based (irreversible) CYP inhibition documented for rolicyclidine creates a pharmacokinetic interaction risk atypical of most recreational dissociativessupported
PCPY and PCP analogues cause mechanism-based CYP inhibition. pmid:2891481
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
Confirmatory identification requires GC-HRMS or targeted LC-MS/MS methodssupported
Novel GC-HRMS method for identification of 30 PCP analogues in blood and urine. j.jchromb.2025.124464
neuroscience5 · 2 ok
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
The structural analogue 4'-F-PCP demonstrates robust self-administration behavior in rodents through dopaminergic mechanisms in the nucleus accumbens, supporting a dopaminergic component to the reinforcing and euphorigenic properties of the arylcyclohexylamine class.supported
4'-F-PCP has high abuse potential via dopaminergic mechanisms in NAc. DAT and D1 receptor expression altered. ijms21134631
The reversal of PHP psychosis by physostigmine in one case report implicates cholinergic neurotransmission in the expression of PCP-class psychotomimesis, though the mechanism remains unclear and the observation has not been replicated.supported
Treatment with physostigmine (IM) produced a rapid and sustained reversal of these symptoms. pmid:7175996
clinical-evidence4 · 3 ok
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Giannini and Castellani (1982) reported a single case of PHP intoxication presenting with psychosis and motor impairmentsupported
A case is presented of a 31-year-old male who showed neurological and psychic symptoms following ingestion of phenylcyclohexylpyrrolidine (PHP). pmid:7175996
Physostigmine administered intramuscularly produced rapid and sustained reversal of symptoms, suggesting anticholinergic-like features in the toxidromesupported
Treatment with physostigmine (IM) produced a rapid and sustained reversal of these symptoms. pmid:7175996
Giannini et al. (1985) published a series of 20 cases of PHP-induced psychosissupported
Twenty white males who presented with psychosis were later found to have ingested PHP. pmid:4057312
comparative-pharmacology4 · 3 ok
The following table summarizes the relative potency ranking from drug discrimination studies in squirrel monkeys:supported
Squirrel monkeys trained to discriminate PCP from saline. Relative potency for drug-lever responding: TCP > PCP = PCE > PHP > PCM > ketamine. pmid:7208560
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
The morpholine analogue 3-MeO-PCMo shows NMDA affinity approximately 12-fold lower than PCPsupported
3-MeO-PCMo has moderate NMDA affinity comparable to ketamine, ~12-fold lower than PCP. dta.2213
Rolicyclidine is distinguished from other PCP analogues by generating the largest proportion of phenylcyclohexylamine (PCA) during alpha-carbon oxidation — a metabolic consequence of the pyrrolidine ring's susceptibility to sequential alpha-hydroxylationsupported
Alpha-hydroxylation is dominant pathway; all congeners form phenylcyclohexylamine (PCA) via second alpha-hydroxylation. Pyrrolidine analogue generated largest proportion of PCA. pmid:2171233
effects-overview4 · 4 ok
The experiential profile is reconstructed entirely from clinical case reports of illicit intoxication and behavioral pharmacology in non-human primatessupported
A case is presented of a 31-year-old male who showed neurological and psychic symptoms following ingestion of phenylcyclohexylpyrrolidine (PHP). pmid:7175996
The experiential profile is reconstructed entirely from clinical case reports of illicit intoxication and behavioral pharmacology in non-human primatessupported
Twenty white males who presented with psychosis were later found to have ingested PHP. pmid:4057312
The experiential profile is reconstructed entirely from clinical case reports of illicit intoxication and behavioral pharmacology in non-human primatessupported
Squirrel monkeys trained to discriminate PCP from saline. PHP and four other analogues generalized to PCP with dose-dependent responding. pmid:7208560
Rolicyclidine's experiential character is expected to fall between ketamine and PCP in intensity at equipotent doses, consistent with its intermediate behavioral potency in the arylcyclohexylamine seriessupported
Relative potency for drug-lever responding: TCP > PCP = PCE > PHP > PCM > ketamine. pmid:7208560
history4 · 1 ok
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Clinical case reports from Giannini and colleagues subsequently documented the drug's psychotomimetic effects and treatment responses: a single case of PHP intoxication treated with physostigmine was reported in 1982, followed by a series of 20 PHP psychosis cases treated with haloperidol in 1985supported
A case is presented of a 31-year-old male who showed neurological and psychic symptoms following ingestion of phenylcyclohexylpyrrolidine (PHP)... Treatment with physostigmine (IM) produced a rapid and sustained reversal. pmid:7175996
receptor-pharmacology4 · 3 ok
The only quantitative potency data derive from drug discrimination studies in squirrel monkeys:supported
Squirrel monkeys trained to discriminate PCP from saline. PHP and four other analogues generalized to PCP with dose-dependent responding. pmid:7208560
TCP > PCP = PCE > PHP (rolicyclidine) > PCM > ketaminesupported
Relative potency for drug-lever responding: TCP > PCP = PCE > PHP > PCM > ketamine. pmid:7208560
Claim in receptor-pharmacology — not_supportednot supportedworking →
Rolicyclidine is thus intermediate in potency among the arylcyclohexylamine series — more potent than ketamine and the morpholine analogue (PCM), less potent than PCP and eticyclidine (PCE)supported
Relative potency for drug-lever responding: TCP > PCP = PCE > PHP > PCM > ketamine. pmid:7208560
chemistry1 · 0 ok
Claim in chemistry — inconclusiveinconclusiveworking →