generation run 2026-05-03
49 min completedmodel pipeline-v5plan not recordedrun/0344bfd2…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
none raised on this run
Reproduce
- inputs
- 15 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
20 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubChem | proscaline | 1 | 1 | Single entry; confirms molecular identity and provides verified chemical data |
| 2 | PubMed | mescaline head twitch response 5-HT2A potency ED50 | 1 | 1 | Critical methodological paper validating HTR assay's predictive validity for human hallucinogenic potency |
| 3 | OpenAlex | proscaline 3,5-dimethoxy-4-propoxyphenethylamine | 1 | 1 | Confirmed primary research source; citation graph revealed unrelated related works |
| 4 | ClinicalTrials.gov · absence | proscaline | 0 | 0 | No results - confirms absence of clinical trial data for this substance |
| 5 | PubMed | proscaline phenethylamine psychedelic | 1 | 1 | Only PubMed result directly studying proscaline; highly relevant for pharmacology and SAR |
| 6 | PubMed | mescaline pharmacokinetics metabolism phenethylamine human | 10 | 3 | Most directly relevant mescaline PK studies; mescaline is the structural parent compound of proscaline |
| 7 | PubMed | mescaline analogs serotonin 5-HT2A receptor binding affinity phenethylamine | 3 | 3 | Selected papers on 5-HT2A binding of mescaline-class phenethylamines relevant to proscaline's pharmacological class |
| 8 | ClinicalTrials.gov · absence | proscaline | 0 | 0 | No trials - confirms absence of formal clinical research |
| 9 | PubMed | new psychoactive substances phenethylamine legal status scheduling analog | 3 | 1 | Swiss scheduling paper provides comparative EU/DACH legal context; NPS review provides broad legal framework |
| 10 | Web | proscaline PiHKAL Shulgin legal status controlled substance | 10 | 2 | Primary source for PiHKAL data on proscaline; confirmed legal status across jurisdictions |
| 11 | PubMed | Nichols psychedelics SAR phenethylamine 5-HT2A mescaline | 2 | 1 | Authoritative SAR review covering mescaline class directly relevant to proscaline |
| 12 | PubMed | hallucinogen persisting perception disorder HPPD phenethylamine psychedelic | 2 | 1 | HPPD risk data for 5-HT2A agonist class; relevant to harm reduction section for proscaline |
| 13 | PubMed | psychedelic cross tolerance 5-HT2A serotonin receptor downregulation | 1 | 1 | Mechanistic data on 5-HT2A tolerance directly relevant to proscaline's tolerance profile |
| 14 | Erowid | proscaline PiHKAL entry #140 | 1 | 1 | Primary source for physical properties, dosage, effects, and synthesis of proscaline |
| 15 | UK Legislation | phenethylamine UK Misuse of Drugs Act Schedule 2 | 1 | 1 | Primary legal source confirming UK Class A status of proscaline via generic phenethylamine clause |
| 16 | Web | proscaline Australia Canada legal status | 10 | 1 | Jurisdictional coverage needed for legal status section |
| 17 | Multiple | Proscaline dose data verification - DB vs PiHKAL vs PsychonautWiki | 3 | 1 | Cross-reference confirmed dose data alignment across sources - no contradictions found |
| 18 | Web | proscaline CAS number 39201-78-0 SMILES InChI | 10 | 3 | Chemical identity data confirmed from multiple independent registry sources |
| 19 | PubMed | phenethylamine 5-HT2B receptor cardiac valvulopathy serotonin agonist risk | 1 | 1 | Cardiac risk context for phenethylamine class |
| 20 | UK Legislation | phenethylamine MDA 1971 Schedule 2 generic clause | 1 | 1 | Primary source confirming UK legal status |
41 claims by section — every cited sentence, checked against its source
safety10 · 5 ok
Claim in safety — inconclusiveinconclusiveworking →
Nausea and emesis are common dose-dependent adverse effects of mescaline, occurring frequently at 800 mg oralsupported
Nausea/emesis at 800mg. s41398-024-03116-2
Hallucinogen Persisting Perception Disorder (HPPD) — persistent visual disturbances following psychedelic use — is documented for the 5-HT₂A agonist class, with case reports involving potent full agonists such as 25I-NBOMesupported
5-HT2A receptor agonists pose risks of acute intoxication and long-term effects including hallucinogen persisting perception disorder (HPPD), derealization, and depersonalization. j.biopha.2021.112295
Tolerance to proscaline's effects develops rapidly through 5-HT₂A receptor density downregulation in frontal cortex, a mechanism demonstrated for the 5-HT₂A agonist class using DOI as a probe compoundsupported
DOI repeated administration induces progressive tolerance to HTR via 5-HT2A downregulation. acschemneuro.2c00170
Full cross-tolerance exists among 5-HT₂A agonist psychedelics, including lsd, psilocybin, mescaline, dmt, and the DOx seriespartially supported
Cross-tolerance between DOI and LSD. Nonpsychedelic 5-HT2A agonist lisuride did not produce cross-tolerance. acschemneuro.2c00170
Claim in safety — not_supportednot supportedworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
5-HT₂A antagonists (ketanserin, haloperidol, risperidone, clozapine) attenuate or block the psychedelic effects of mescaline-class compounds, confirmed in controlled human studies.partially supported
5-HT2A mediation confirmed via ketanserin. s41398-024-03116-2
Claim in safety — inconclusiveinconclusiveworking →
pharmacology7 · 5 ok
The mouse head-twitch response (HTR) — a behavioral readout mediated exclusively by 5-HT₂A activation and abolished by selective antagonists such as ketanserin and M100907 — is reliably elicited by proscalinesupported
HTR dose-response experiments with mescaline, escaline and proscaline in C57BL/6J mice. 0269881119826610
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
For the 3,4,5-substituted phenethylamine series, conformational mobility of the 3- and 5-methoxy groups is required for receptor activation, as demonstrated by conformationally restricted analogs that lose activity when ring rotation is preventedsupported
3,4,5-trioxygenated analogs require conformationally mobile 3 and 5 methoxy groups. pmid:9301661
In a randomized, double-blind, placebo-controlled crossover study (n = 16), oral mescaline showed dose-proportional pharmacokinetics across 100–800 mg, with a Tmax of approximately 2 hours, a plasma elimination half-life of approximately 3.5 hours, and subjective effect durations of 6.4–14 hours (dose-dependent).supported
RCT in 16 subjects. Mescaline 100-800mg. Tmax ~2h, plasma half-life ~3.5h. Duration 6.4-14h dose-dependent. s41398-024-03116-2
Mescaline undergoes three principal metabolic transformations:supported
LC-MS/MS method for mescaline and metabolites TMPAA, NAM, 4-desmethyl mescaline in human plasma. j.jpba.2022.114980
Mescaline undergoes three principal metabolic transformations:supported
Review of mescaline PK/PD, mechanism of action, metabolism, duration, clinical and forensic aspects. 1874467211666181010154139
receptor-pharmacology6 · 5 ok
Proscaline's psychedelic activity is mediated by 5-HT₂A agonism, confirmed behaviorally through the HTR assaysupported
HTR dose-response experiments with mescaline, escaline and proscaline in C57BL/6J mice. Potency relationships closely parallel human hallucinogenic data. 0269881119826610
The α-methyl analog 3C-P demonstrates higher intrinsic activity at 5-HT₂A-coupled phospholipase C signaling relative to the parent phenethylamine proscaline, consistent with the general finding that α-methylation increases functional efficacy at this receptor.supported
Alpha-methylation increases intrinsic activity significantly. pmid:16277614
Homology modeling and SAR studies of the mescaline class indicate that conformational freedom of the 3- and 5-methoxy substituents is required for productive binding at the 5-HT₂A orthosteric sitesupported
3,4,5-trioxygenated analogs require conformationally mobile 3 and 5 methoxy groups. pmid:9301661
Claim in receptor-pharmacology — not_supportednot supportedworking →
Proscaline retains this conformational mobility; its enhanced potency relative to mescaline in the HTR assay is attributed to the increased lipophilicity and steric properties of the 4-propoxy group.supported
Replacing 4-methoxy with ethoxy or propoxy increases potency. 0269881119826610
Sustained 5-HT₂B agonism is associated with cardiac valvulopathy, as documented with fenfluramine and related compoundssupported
5-HT hypothesis for fenfluramine-induced valvular heart disease. 5-HT2B receptor agonism linked to cardiac risk. 14740330902931524
comparative-pharmacology5 · 3 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Halberstadt et al. (2019) established the relative potency order of 3,4,5-substituted phenethylamines in the mouse HTR assay: proscaline (4-propoxy) > escaline (4-ethoxy) > mescaline (4-methoxy)supported
HTR dose-response experiments with mescaline, escaline and proscaline in C57BL/6J mice. Replacing 4-methoxy with ethoxy or propoxy increases potency. 0269881119826610
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
The translational validity of mouse HTR data for predicting human hallucinogenic potency is supported by a strong correlation (r = 0.9448) across 41 compoundssupported
Strong positive correlation r=0.9448 between mouse HTR and human hallucinogenic potency. Supports translational relevance of HTR assay. j.neuropharm.2019.107933
The α-methyl analog of proscaline (3C-P) shows higher intrinsic activity at 5-HT₂A-coupled phospholipase C activation. α-Methylation generally increases oral bioavailability (through resistance to MAO-mediated first-pass deamination), duration of action, and functional efficacy at 5-HT₂Apartially supported
Alpha-methylation increases intrinsic activity significantly. pmid:16277614
summary5 · 4 ok
Active at oral doses of 30–60 mg, it produces effects lasting 8–12 hours — comparable to mescaline in duration but substantially greater in potency per milligram, as confirmed in the mouse head-twitch response (HTR) assay.partially supported
HTR dose-response experiments with mescaline, escaline and proscaline in C57BL/6J mice. Replacing 4-methoxy with ethoxy or propoxy increases potency. 0269881119826610
A single peer-reviewed behavioral study confirmed increased HTR potency relative to mescaline in micesupported
HTR dose-response experiments with mescaline, escaline and proscaline in C57BL/6J mice. Replacing 4-methoxy with ethoxy or propoxy increases potency. 0269881119826610
As a 3,4,5-trisubstituted phenethylamine, proscaline is presumed to act primarily through 5-HT₂A receptor agonism — the established mechanism for psychedelic effects in this structural classsupported
Reviews SAR for classic serotonergic hallucinogens (tryptamines, ergolines, phenethylamines). 5-HT2A as principal target. Key structural features for activity discussed including the 3,4,5-trimethoxyphenethylamine (mescaline) class. 7854_2017_475
Tolerance develops rapidly through 5-HT₂A receptor downregulation in frontal cortex, with full cross-tolerance to other serotonergic psychedelics; the compound is not considered habit-formingsupported
DOI repeated administration induces progressive tolerance to HTR via 5-HT2A downregulation. Cross-tolerance between DOI and LSD. acschemneuro.2c00170
Claim in summary — inconclusiveinconclusiveworking →
pharmacokinetic-detail4 · 4 ok
Mescaline is well absorbed orally, with dose-proportional kinetics across the 100–800 mg range and a Tmax of approximately 2 hourssupported
Mescaline 100-800mg. Tmax ~2h. s41398-024-03116-2
Mescaline's three major metabolic routes — N-acetylation, O-demethylation, and MAO-A-mediated oxidative deamination — are documented analyticallysupported
LC-MS/MS method for mescaline and metabolites TMPAA, NAM, 4-desmethyl mescaline in human plasma. j.jpba.2022.114980
Mescaline's three major metabolic routes — N-acetylation, O-demethylation, and MAO-A-mediated oxidative deamination — are documented analyticallysupported
Review of mescaline PK/PD, mechanism of action, metabolism, duration, clinical and forensic aspects. 1874467211666181010154139
Mescaline's plasma elimination half-life is approximately 3.5 hours, yet subjective effects persist 6.4–14 hours (dose-dependent)supported
Plasma half-life ~3.5h. Duration 6.4-14h dose-dependent. s41398-024-03116-2
chemistry1 · 1 ok
The α-methyl (amphetamine) homologue of proscaline is 3C-P, which shares the same ring substitution pattern but incorporates an additional methyl group on the side chain α-carbon, conferring increased intrinsic activity at 5-HT₂A-mediated phospholipase C signaling.supported
Alpha-methylation increases intrinsic activity significantly. pmid:16277614
history1 · 1 ok
The sole formal pharmacological study — Halberstadt et al. (2019) — measured proscaline's behavioral potency in mice as part of a broader structure-activity relationship investigation of mescaline analogs, confirming greater HTR potency than both mescaline and escaline.supported
HTR dose-response experiments with mescaline, escaline and proscaline in C57BL/6J mice. Replacing 4-methoxy with ethoxy or propoxy increases potency. 0269881119826610
legal-status1 · 1 ok
Proscaline's direct structural derivation from mescaline — differing only in the 4-position alkoxy group — and its confirmed 5-HT₂A agonist activity would likely satisfy both criteriasupported
HTR dose-response experiments with mescaline, escaline and proscaline in C57BL/6J mice. Potency relationships closely parallel human hallucinogenic data. 0269881119826610
neuroscience1 · 0 ok
Claim in neuroscience — inconclusiveinconclusiveworking →