PCE

# Research Output: PCE (Eticyclidine)

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## ⚠️ CRITICAL FLAG — Database Error in Seed Data

The brief's "systematic name" field contains **"1,1,2,2-tetrachloroethene"** — this is **tetrachloroethylene**, an industrial solvent and dry-cleaning chemical (CAS 127-18-4). It has absolutely no pharmacological relationship to PCE the drug. This is a severe database error that must be corrected before generation. The correct systematic name for PCE is **N-ethyl-1-phenylcyclohexan-1-amine** (IUPAC). All chemical identity data below is confirmed from PubChem CID 16622 and Crossref-verified sources.

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## Chemical Identity

**Confirmed from PubChem CID 16622 [Ref 9 via API]:**

- **Common name**: PCE; Eticyclidine
- **Development code**: CI-400 (Parke-Davis)
- **CAS number**: 2201-15-2 (confirmed: Wikidoc [Ref 9], Pelletier et al. 2022 [Ref 25])
- **IUPAC name**: N-ethyl-1-phenylcyclohexan-1-amine
- **Molecular formula**: C₁₄H₂₁N
- **Molecular weight**: 203.32 g/mol
- **SMILES**: CCNC1(CCCCC1)c1ccccc1
- **InChIKey**: IFYLVUHLOOCYBG-UHFFFAOYSA-N
- **PubChem CID**: 16622
- **Chemical class**: Arylcyclohexylamine

**Discrepancies with brief:**
- CRITICAL: "Systematic name" field lists tetrachloroethylene (PCE the solvent) — must be replaced with "N-ethyl-1-phenylcyclohexan-1-amine"
- SMILES field is empty — should be populated: CCNC1(CCCCC1)c1ccccc1
- Molecular formula empty — C₁₄H₂₁N
- Molecular weight empty — 203.32 g/mol
- InChIKey empty — IFYLVUHLOOCYBG-UHFFFAOYSA-N
- PubChem CID empty — 16622

**Physical properties:** No experimentally measured melting point, boiling point, solubility, pKa, or logP data were identified in peer-reviewed literature for PCE specifically. The HCl salt (CAS 1867-64-7) is the form sold as an analytical reference standard by Cayman Chemical [web-retrieved]. PCE is lipophilic by structural inference (arylcyclohexylamine with high logP by analogy to PCP).

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## Pharmacology

### Mechanism of Action

PCE is a non-competitive, open-channel blocker at the N-methyl-D-aspartate (NMDA) glutamate receptor, binding to the PCP site within the ion channel (Maragos et al. 1988 [Ref 3]; Jentsch & Roth 1999 [Ref 2]). This site is accessible only when the channel is open (use-dependent block), making PCE a trapping blocker similar to PCP and MK-801 (Bolshakov et al. 2003 [Ref 8 by analogy]).

In addition to NMDA antagonism, PCE acts as a **dopamine, noradrenaline, and serotonin reuptake inhibitor**, and as an **agonist at sigma-1 and sigma-2 receptors** (Coppola & Mondola 2013 [Ref 6]; Pelletier et al. 2022 [Ref 25]). Possible weak mu-opioid receptor affinity has been noted as a class property for arylcyclohexylamines (Hustveit et al. 1995 [Ref 35]), though direct data for PCE specifically is absent.

### Binding Affinities

**No published Ki or IC50 values for PCE itself at any receptor target have been identified in the primary literature.** The following is inferred from class-level and structural-analog data:

- **NMDA receptor (PCP site)**: PCE is described as "one of the most potent arylcyclohexylamines" (Owens et al. 1988 [Ref 1]). Behavioral potency in rats was comparable to PCP despite lower in vitro MK-801 binding site affinity (Cho et al. 1991 [Ref 14]). The discrepancy between in vitro binding and in vivo potency is partially explained by PCE's slower metabolic clearance relative to PCP (Chakrabarti & Law 1983 [Ref 11]).
- **Relative to PCP**: PCE produces full PCP-like discriminative stimulus effects in all subjects in drug discrimination studies (Berquist et al. 2018 [Ref 19]). PCE is described consistently as slightly more potent than PCP in vivo based on user reports and animal behavioral data [Ref 29].
- **Dopamine transporter**: Reuptake inhibition confirmed at class level for arylcyclohexylamines (Jentsch & Roth 1999 [Ref 2]; Pelletier et al. 2022 [Ref 25]).
- **Sigma receptors**: Agonist activity at sigma-1/sigma-2 receptors confirmed at class level (Pelletier et al. 2022 [Ref 25]).

**FLAG**: No substance-specific binding affinity data (Ki/IC50) for PCE is available in published literature. All potency claims rely on behavioral animal studies or class inference.

### Pharmacokinetics

All pharmacokinetic data are from animal (rat) studies unless noted.

**Distribution:**
- PCE is highly lipophilic (arylcyclohexylamine structural class), with expected high volume of distribution. By analogy with PCP (Vd ~6.2 L/kg; Bey & Patel 2007 [Ref 27]), PCE distributes extensively into tissues.
- At 1 week post-dosing, significantly more ³H-label remained in rat tissues from PCE-treated animals than PCP-treated animals, indicating greater tissue sequestration (Chakrabarti & Law 1983 [Ref 11]).

**Elimination:**
- PCE is metabolized and excreted **more slowly than PCP** in rats. Within 1 week of i.v. administration (single 1.09 µmol dose), ~93% of [³H]PCP but only ~65% of [³H]PCE was excreted via urine and feces (Chakrabarti & Law 1983 [Ref 11]).
- The authors attribute PCE's higher psychotropic effects to this slower elimination.
- PCE is itself a metabolite of phenylcyclohexyldiethylamine (PCDE, the N,N-diethyl analog), with saturable conversion from PCDE to PCE and PCE to phenylcyclohexylamine (PCA) (Cho et al. 1993 [Ref 17]).

**Pulmonary first-pass (relevant to smoked ROA):**
- In the rat isolated perfused lung, the lung accumulates at least 20% of administered radioactivity and metabolizes more than 30% of administered PCE or PCP (Law & Chakrabarti 1985 [Ref 16]).
- Pretreatment with 3-methylcholanthrene (3-MC) or cigarette smoke **significantly enhanced PCE metabolism** by the lung and increased conjugated PCE metabolite concentrations in the perfusate (Law & Chakrabarti 1985 [Ref 16]). This is clinically relevant given that smoked use is a known ROA for PCE.

**Metabolic pathway:**
- Primary hepatic metabolism by hydroxylation followed by conjugation (glucuronidation), consistent with PCP class (Mozayani 2003 [Ref 28]).
- PCE is N-deethylated to PCA (phenylcyclohexylamine) as a primary metabolic step (Cho et al. 1993 [Ref 17]).
- CYP2B6 is the primary CYP enzyme responsible for aliphatic hydroxylations in the related 3-MeO-PCP; CYP2D6 also involved (Michely et al. 2017 [Ref 24]). By structural analogy, CYP2B6 and CYP2D6 are likely involved in PCE metabolism. PCE metabolism is inducible by CYP inducers (Law & Chakrabarti 1985 [Ref 16]).

**PCP-class reference pharmacokinetics (applicable to PCE by analogy):**
- Volume of distribution: ~6.2 L/kg (Bey & Patel 2007 [Ref 27])
- Elimination half-life: ~17.6 hours in humans for PCP (Bey & Patel 2007 [Ref 27]); PCE likely has a longer effective half-life due to slower metabolism
- 90% hepatic metabolism (Bey & Patel 2007 [Ref 27])
- Renal excretion is pH-dependent: alkaline urine reduces PCE excretion; acidification increases excretion (Perez-Reyes et al. 1982 [Ref 26])

**No human pharmacokinetic studies on PCE were identified. All human-applicable data is extrapolated from PCP class data.**

### Stereochemistry

PCE (N-ethyl-1-phenylcyclohexan-1-amine) has no stereocenters. The nitrogen is a tertiary amine; the quaternary cyclohexane carbon bonded to phenyl and ethylamino groups is not a stereocenter. No stereochemical complexity identified.

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## History

**Synthesis and discovery:**
PCE belongs to the 1-phenylcycloalkylamine class first systematically studied by Kalir et al. (1969) [Ref 18], who synthesized a series of N,N-substituted 1-arylcyclohexylamines and evaluated their psychopharmacological properties (Journal of Medicinal Chemistry, DOI: 10.1021/jm00303a030, Crossref-verified). Pelletier et al. (2022) [Ref 25] note that PCE and related derivatives were first observed in the **1960s**, at approximately the same time as ketamine.

**Parke-Davis development:**
PCE was developed by Parke-Davis and assigned the development code **CI-400** [Ref 9, Ref 29]. It was evaluated for its anesthetic potential but research was discontinued in favour of ketamine, which offered a more favorable therapeutic profile [Ref 9]. The compound was considered too powerful for clinical development [Ref 25].

**Street emergence:**
PCE was first **identified as a street drug** in a 1978 forensic report by Bailey [Ref 12] (Journal of Pharmaceutical Sciences, DOI verified). Bailey & Legault (1979) [Ref 13] subsequently published reference spectroscopic data (IR, MS, GC, TLC) for N-ethyl-1-phenylcyclohexylamine and related analogs to assist forensic identification.

Fewer than 30 different PCP analogs were reported in street use during the 1970s and 1980s mainly in the United States; PCE was among only a handful (alongside TCP and PCPy/rolicyclidine) that saw any meaningful level of use (Wallach & Brandt 2018 [Ref 20]; UNODC [Ref 10]).

**Decline:**
Despite being slightly more potent than PCP, PCE's **unpleasant taste and strong tendency to cause nausea** made it less accepted by users. It never achieved the level of street prevalence of PCP itself [Ref 9]. Street use declined through the 1980s alongside the broader PCP market. PCE has seen minimal contemporary use as an NPS, with derivatives like 3-MeO-PCE and O-PCE attracting more recent interest in research chemical markets.

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## Subjective Effects

Published controlled human studies on PCE's subjective effects **do not exist**. The following is derived from animal behavioral studies and class-level data.

**Animal behavioral data (direct PCE studies):**
- In PCP-trained rats, **PCE produced full PCP-lever selection in all subjects**, confirming PCE has PCP-like interoceptive (subjective) effects (Berquist et al. 2018 [Ref 19]).
- PCE and PCP both elicited **dose-dependent hypothermia** in mice; **unlike PCP, PCE did not produce locomotor stimulation** in mice (Berquist et al. 2018 [Ref 19]).
- Ataxia and other PCP-characteristic behaviors observed in rats at equivalent doses (Cho et al. 1991 [Ref 14]).
- PCE CSF concentrations correlated with ataxia intensity; increased CSF-PCE was associated with increased ataxic response (Cho et al. 1993 [Ref 15]).

**Class-level subjective effects (PCP analog, human data):**
Intoxication at 2–5 mg PCP-equivalent doses: mild effects (cognitive disturbances, numbness, analgesia). 5–25 mg: dissociation, stupor, coma-like states. >25 mg: deep coma, seizures, death risk (Bey & Patel 2007 [Ref 27], applicable by structural analogy).

Effects characteristic of PCP class: hallucinations, delirium, disorientation, agitation, muscle rigidity, ataxia, nystagmus, seizures, amnesia, analgesia (Mozayani 2003 [Ref 28]; Baldridge & Bessen 1990 [Ref 21]).

**Community-reported effects specific to PCE [Ref 29]:**
- PCE is reported to carry a **significantly higher rate of psychosis and mania** than other dissociatives
- Warning against high-dose or consecutive-day use
- Nausea and unpleasant taste documented as distinguishing features relative to PCP

**Duration data (from database, unverified in primary literature):**
- Oral: onset 30–90 min, peak 2–3h, total 4–8h
- Smoked: onset 2–20 min, peak 2–3h, total 4–6h
- Insufflated: onset 3–30 min, peak 2–3h, total 4–6h
These are consistent with PCP-class pharmacokinetics and plausible given known half-life.

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## Safety & Toxicity

### Acute Toxicity
**No LD50 data for PCE specifically were identified in the literature.** PCP-class compounds have well-documented acute toxicity thresholds by dose in humans (Bey & Patel 2007 [Ref 27]):
- 2–5 mg (PCP): mild intoxication
- 5–25 mg (PCP): stupor, unresponsiveness
- >25 mg (PCP): deep coma, seizures, death

PCE is described as slightly more potent than PCP; acute toxic doses may be proportionally lower.

### Adverse Effects

**PCP-class acute complications** (applicable to PCE):
- Rhabdomyolysis (skeletal muscle breakdown)
- Seizures
- Hyperthermia
- Psychosis
- Cardiovascular complications (hypertension, tachycardia)
- Respiratory depression at high doses
(Baldridge & Bessen 1990 [Ref 21]; Mozayani 2003 [Ref 28])

**PCE-specific reported adverse effects:**
- Significantly higher rate of **psychosis and mania** than other dissociatives [Ref 29] — this is a community-observed pattern with no published clinical validation
- Nausea (documented historically as reason for limited street uptake)
- Unpleasant taste

**Long-term risks (PCP-class, applicable by analogy):**
- Schizophrenia-like psychotic episodes
- Severe lasting memory loss
- Disorganized thinking
- Depression
- Weight loss
- Liver abnormalities
- Rhabdomyolysis
(Bey & Patel 2007 [Ref 27]; Jentsch & Roth 1999 [Ref 2])

### Organ Toxicity
No organ-specific toxicity data for PCE published. Pulmonary first-pass metabolism is significant for the smoked route (Law & Chakrabarti 1985 [Ref 16]).

### Chronic Toxicity
Described as "moderate" in the brief with note "Inferred from pharmacological class — not sourced from literature." No published chronic toxicity studies for PCE specifically. Classification as moderate for both acute and chronic toxicity is consistent with PCP-class designations but not directly confirmed by PCE-specific studies.

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## Harm Reduction

### General
- PCE is significantly more potent than PCP; doses should be treated conservatively
- Volumetric liquid dosing recommended due to potency (common doses in low milligram range) [Ref 29]
- Avoid consecutive-day use due to psychosis/mania risk [Ref 29]
- No published clinical harm reduction protocols specific to PCE

### Drug Interactions
**Depressants (alcohol, benzodiazepines, opioids, GHB):**
- Combined CNS depression with respiratory depression risk; risk of sudden loss of consciousness, vomiting while unconscious, and aspiration — class-level warning applicable to all NMDA antagonists [Ref 29]

**Stimulants:**
- Combination with stimulants may increase cardiovascular strain and psychosis risk [Ref 29]

**Other dissociatives:**
- Additive NMDA antagonism; increased risk of amnesia, psychosis, respiratory depression

**No published clinical interaction studies for PCE identified.**

### Clinical Management of Overdose (PCP-class)
- Benzodiazepines for agitation and seizure control (Bey & Patel 2007 [Ref 27])
- Activated charcoal if ingested and airway is secure (Bey & Patel 2007 [Ref 27])
- Urine acidification (ammonium chloride) and forced diuresis increase renal clearance — pH-dependent excretion demonstrated for PCP class (Perez-Reyes et al. 1982 [Ref 26]); caution due to rhabdomyolysis risk with acidification
- Avoid antipsychotics (lowered seizure threshold)
- Supportive care: temperature management, cardiovascular monitoring

### Testing and Identification
- PCE was first analytically identified by Bailey (1978) [Ref 12] using spectroscopic techniques
- Reference IR, MS, GC, TLC data published by Bailey & Legault (1979) [Ref 13]
- Standard PCP immunoassay screens may not detect PCE; cross-reactivity variable
- GC-MS and LC-MS/MS methods exist for arylcyclohexylamines (Pelletier et al. 2022 [Ref 25])

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## Tolerance & Dependence

### Tolerance
**No published tolerance studies for PCE specifically.** PCP-class tolerance:
- Repeated administration produces tolerance to behavioural effects (class-level inference)
- Cross-tolerance within dissociative class expected (NMDA antagonist mechanism)
- Database values (buildup with prolonged use; half-life 5 days; full reset 1.5 weeks) are consistent with PCP-class inference but not sourced from PCE-specific data

**FLAG**: Tolerance half-life of "5 days" in the database is unverified against primary literature for PCE. It may be a reasonable class inference, but must be labelled as such.

### Dependence Liability
**High physical and psychological dependence potential** attributed based on pharmacological class (Pelletier et al. 2022 [Ref 25]). Database states "highly addictive with a high potential for adverse side effects such as psychosis" — this is pharmacological class inference, not a PCE-specific clinical finding.

No published human dependence or withdrawal case studies for PCE identified.

PCP class: reinforcing effects demonstrated in animal self-administration models. MXE (a close structural analog) was a less effective reinforcer than PCP in rat self-administration (Berquist et al. 2018 [Ref 19]).

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## Interactions

Published PCE-specific drug interaction data: **none identified**.

All data below is class-level inference from PCP pharmacology:

| Interaction | Mechanism | Risk Level |
|-------------|-----------|------------|
| CNS depressants (alcohol, benzodiazepines, opioids, GHB) | Additive respiratory depression | High |
| Stimulants (amphetamines, cocaine) | Cardiovascular strain; psychosis potentiation | High |
| Other dissociatives | Additive NMDA antagonism | Moderate-High |
| MAOIs | Unknown; avoid — serotonin reuptake inhibition of PCE raises concern | Unknown |
| Antipsychotics | Theoretical antagonism of dopamine effects; seizure threshold changes | Unknown |

CYP interactions: CYP2B6 and CYP2D6 inducers (e.g., rifampicin, carbamazepine) may increase PCE metabolism based on class analogy (Michely et al. 2017 [Ref 24]; Law & Chakrabarti 1985 [Ref 16]).

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## Legal Status

| Jurisdiction | Status | Schedule/Class | Notes |
|---|---|---|---|
| United States | Illegal | Schedule I (CSA) | Placed Schedule I in 1970s due to PCP similarity |
| United Kingdom | Illegal | Class A | Misuse of Drugs Act 1971 (Modification) Order 1984 [Ref 30] |
| Canada | Illegal | Schedule I (CDSA) | Listed as N-(1-phenylcyclohexyl)ethylamine [Ref 31] |
| Australia | Controlled | Narcotic | Import/export licensing required [Ref 32] |
| International | Controlled | 1971 UN Convention Schedule I | Together with PCP, TCP, PCPy [Ref 10] |
| Germany | Controlled | BtMG Anlage I (inferred) | Listed as controlled dissociative; exact Anlage not confirmed from primary source |
| EU (general) | Monitored | 3-MeO-PCE reported to EMCDDA Early Warning System 2010; PCE itself covered by 1971 Convention |

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## Clinical Trials

**No clinical trials registered on ClinicalTrials.gov for PCE (eticyclidine).** Search returned zero results. PCE has never been investigated in human clinical trials.

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## Community Feedback Analysis

**No community feedback was submitted** in Part A2 of the brief. No community feedback items to analyze.

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## Gaps & Flags

### CRITICAL (must fix before generation)

1. **⛔ SEVERE DATABASE ERROR**: The brief lists "systematic name: 1,1,2,2-tetrachloroethene" — this is tetrachloroethylene (PCE the solvent, CAS 127-18-4), an entirely different compound. The correct IUPAC name is **N-ethyl-1-phenylcyclohexan-1-amine**. This error must be corrected in the database before the article generates.

2. **Missing chemical fields**: SMILES, molecular formula, molecular weight, InChIKey, and PubChem CID fields are all empty in the DB. All confirmed from PubChem API and should be populated.

### Pharmacology Gaps

3. **No PCE-specific binding affinity data (Ki/IC50)**: No published Ki or IC50 values for PCE at NMDA, sigma, dopamine transporter, or any other receptor exist in the literature. All receptor binding data is class-level inference from PCP or structural analogs. This section must explicitly note absence of substance-specific binding data.

4. **No human pharmacokinetic studies**: All PK data is from rat studies (Chakrabarti & Law 1983; Law & Chakrabarti 1985; Cho et al. 1991, 1993). Human half-life, bioavailability, Tmax, Cmax, and protein binding are unknown for PCE.

5. **Behavioral potency discrepancy**: Cho et al. (1991) found PCE behavioral potency comparable to PCP despite lower MK-801 binding site affinity. However, Owens et al. (1988) calls PCE "one of the most potent arylcyclohexylamines." These are not necessarily contradictory (in vivo vs. in vitro) but require careful framing.

### Safety Gaps

6. **No LD50 data for PCE**: Acute toxicity threshold unknown from substance-specific literature.

7. **Psychosis/mania risk claim**: PsychonautWiki states PCE carries a "significantly higher rate" of psychosis and mania than other dissociatives. This is a community observation with no published clinical validation. Should be noted as user-report-only.

8. **Dependence data not sourced**: Database values for dependence (high physical/psychological) are class-level inferences, not PCE-specific clinical findings. Should be framed as "inferred from pharmacological class."

9. **Tolerance half-life (5 days)**: Unverified against primary literature. Class inference only. Must be labelled as such.

### Legal Status Gaps

10. **Germany exact Anlage**: Could not confirm specific Anlage classification (I, II, or III) from primary German legislative source. All web sources confirm controlled status under BtMG; Anlage I is most likely given Schedule I status internationally.

11. **EU member state harmonization**: PCE is covered by the 1971 UN Convention (Schedule I), so EU member states should all control it, but individual implementing legislation was not verified for each country.

### Dose/Duration Notes

12. **Dose data (existing DB values)**: Threshold/Light/Common/Strong ranges exist in the database and are internally consistent with PCP-class potency expectations. No published controlled human dose studies exist for PCE. These values should be retained with "community consensus" provenance label and flagged as unverified against clinical literature.

13. **Duration data**: The DB duration values (total 4–8h oral, 4–6h smoked/insufflated) are plausible given PCP-class pharmacokinetics and PCE's known slower metabolism. No published human duration studies exist.