generation run 2026-05-03
56 min completedmodel pipeline-v5plan not recordedrun/ec72b74f…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
none raised on this run
Reproduce
- inputs
- 17 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
21 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubChem | escaline | 1 | 1 | Primary chemical identity verification |
| 2 | PsychonautWiki | escaline dosage duration pharmacology | 1 | 1 | Community-derived dose data for comparison with PiHKAL |
| 3 | Erowid PiHKAL online | escaline PiHKAL entry | 1 | 1 | Primary source for synthesis history and qualitative effects |
| 4 | OpenAlex | escaline 4-ethoxy-3,5-dimethoxyphenethylamine psychedelic | 4 | 1 | Only direct escaline paper in results |
| 5 | WebSearch | escaline PiHKAL Shulgin phenethylamine #38 synthesis history | 10 | 2 | Primary historical and dosage data |
| 6 | PubMed | mescaline analog serotonin receptor binding affinity phenethylamine 5-HT2A | 9 | 3 | Relevant to 5-HT2A pharmacology of mescaline class |
| 7 | ClinicalTrials.gov · absence | escaline mescaline analog phenethylamine psychedelic | 0 | 0 | N/A - no results |
| 8 | PubMed | escaline phenethylamine psychedelic pharmacology | 2 | 2 | Both directly relevant to escaline pharmacology |
| 9 | PubMed | mescaline human pharmacokinetics bioavailability metabolism plasma half-life | 1 | 1 | Most current human PK data for mescaline class - relevant proxy for escaline |
| 10 | NCATS Inxight Drugs | — | 1 | 1 | Critical receptor binding data for escaline |
| 11 | PubMed | receptor interaction profiles 4-alkoxy-3,5-dimethoxy phenethylamines mescaline derivatives 2021 | 1 | 1 | Key pharmacological paper for escaline's receptor class |
| 12 | WebSearch | escaline DEA schedule I 7930 controlled substance analog mescaline | 10 | 1 | Legal status data across jurisdictions |
| 13 | PubMed | phenethylamine hallucinogen tolerance cross-tolerance serotonin 5-HT2A receptor downregulation | 1 | 1 | Provides mechanistic basis for psychedelic class tolerance |
| 14 | PubMed/WebSearch | Blaazer Smid Kruse 2008 ChemMedChem phenylalkylamine 5-HT2A escaline | 1 | 1 | Primary source for escaline binding affinity data |
| 15 | WebSearch | escaline DEA schedule I 7930 legal status US Sweden Germany Canada | 1 | 1 | Multi-jurisdiction legal status determination |
| 16 | PubMed | Nichols 1977 lipophilicity serotonin agonist activity mescaline analogs 4-substituted | 1 | 1 | Foundational pharmacological paper for escaline class |
| 17 | PubMed | tramadol serotonin syndrome mechanism serotonin reuptake inhibition opioid | 1 | 1 | Explains mechanistic basis for dangerous tramadol + escaline interaction |
| 18 | PubMed | mescaline peyote drug discrimination psychedelic cross-tolerance clinical pharmacology | 1 | 1 | Authoritative review for class pharmacology context |
| 19 | WebSearch | Mueller 2025 mescaline pharmacokinetics Tmax half-life healthy volunteers | 5 | 1 | Most current mescaline PK data as reference for escaline |
| 20 | PubMed | mescaline acute effects dose-dependent double-blind placebo-controlled healthy subjects 2024 | 1 | 1 | Primary clinical pharmacology reference for mescaline as escaline analog |
| 21 | PubMed | mescaline LSD psilocybin comparative randomized double-blind placebo cross-over healthy | 1 | 1 | Comparative clinical pharmacology providing reference context for mescaline/escaline class |
66 claims by section — every cited sentence, checked against its source
pharmacology16 · 7 ok
Its psychedelic effects are mediated primarily through agonism at the 5-HT₂A receptor, consistent with all phenethylamine-class hallucinogenssupported
Comprehensive review of 5-HT2A receptor as primary site of hallucinogen action. j.bbr.2014.07.016
Its psychedelic effects are mediated primarily through agonism at the 5-HT₂A receptor, consistent with all phenethylamine-class hallucinogenssupported
5-HT2A as principal target. Key structural features for each class. 7854_2017_475
This mechanism is confirmed by class studies demonstrating that the selective 5-HT₂A antagonist ketanserin substantially attenuates the psychedelic effects of mescaline — the closest well-studied structural analog — in controlled human trials.supported
Ketanserin attenuated effects confirming 5-HT2A as primary mechanism. s41398-024-03116-2
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
In the murine head-twitch response (HTR) assay — a validated behavioral model of 5-HT₂A-mediated psychedelic activity — escaline produces responses with greater potency than mescaline, and potency relationships closely parallel human hallucinogenic datasupported
Homologation of 4-methoxy to ethoxy (escaline) or propoxy (proscaline) increased potency in HTR. Potency relationships closely parallel human hallucinogenic data. 0269881119826610
Claim in pharmacology — inconclusiveinconclusiveworking →
Mescaline exhibits an oral Tmax of approximately 2 hours, a plasma elimination half-life of approximately 3.5 hours, and dose-proportional pharmacokinetics from 100–800 mgsupported
Dose-proportional PK. Tmax ~2h, t1/2 ~3.5h. s41398-024-03116-2
Claim in pharmacology — inconclusiveinconclusiveworking →
Mescaline exhibits an oral Tmax of approximately 2 hours, a plasma elimination half-life of approximately 3.5 hours, and dose-proportional pharmacokinetics from 100–800 mgsupported
Dose-proportional PK. Tmax ~2h, t1/2 ~3.5h. s41398-024-03116-2
Mescaline exhibits an oral Tmax of approximately 2 hours, a plasma elimination half-life of approximately 3.5 hours, and dose-proportional pharmacokinetics from 100–800 mgpartially supported
RCT comparing mescaline (300/500 mg)... Plasma t1/2 ~3.5h. s41386-023-01607-2
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
safety11 · 10 ok
Mescaline produces dose-dependent increases in systolic and diastolic blood pressure and heart rate in controlled human trialssupported
Dose-proportional PK...Increased blood pressure and heart rate. s41398-024-03116-2
Mescaline produces emesis particularly at high dosessupported
Nausea/emesis at 800 mg. s41398-024-03116-2
Repeated administration of 5-HT₂A psychedelics produces rapid tolerance via receptor downregulation in the frontal cortexsupported
Tolerance via 5-HT2A receptor downregulation in frontal cortex. acschemneuro.2c00170
Tolerance develops within 24 hours of a single administration and is mediated by 5-HT₂A receptor internalization rather than beta-arrestin-2 signaling.partially supported
Tolerance via 5-HT2A receptor downregulation in frontal cortex. Beta-arrestin-2 knockout does not prevent tolerance. acschemneuro.2c00170
Bidirectional cross-tolerance exists between serotonergic hallucinogens, meaning recent use of lsd, psilocybin, or mescaline will diminish escaline's effectssupported
Cross-tolerance among serotonergic hallucinogens. j.bbr.2014.07.016
Bidirectional cross-tolerance exists between serotonergic hallucinogens, meaning recent use of lsd, psilocybin, or mescaline will diminish escaline's effectssupported
Cross-tolerance between DOI and LSD. acschemneuro.2c00170
Cross-tolerance with nonpsychedelic 5-HT₂A agonists (e.g., lisuride) was not observed in murine studies, suggesting psychedelic-specific tolerance mechanisms.supported
Nonpsychedelic 5-HT2A agonists do not produce cross-tolerance. acschemneuro.2c00170
Tramadol inhibits the serotonin reuptake transporter (SERT) in vitro and possesses weak 5-HT₂A agonist propertiessupported
Tramadol inhibits human SERT in vitro...Reviews mechanism of tramadol as SERT inhibitor and 5-HT2A agonist. s00204-018-2244-6
Claim in safety — not_supportednot supportedworking →
Escaline's expected dose-dependent blood pressure and heart rate elevation poses risk of hypertensive crisis or cardiac events in individuals with pre-existing cardiovascular compromise.supported
Increased blood pressure and heart rate. s41398-024-03116-2
Concurrent serotonergic medication — MAOIs, SSRIs, SNRIs, and tramadol — is contraindicated due to serotonin syndrome risk.supported
Combined with serotonergic drugs, tramadol precipitates serotonin syndrome. s00204-018-2244-6
summary10 · 7 ok
Claim in summary — inconclusiveinconclusiveworking →
First synthesized by Benington, Morin, and Clark in 1954, escaline received its first systematic pharmacological characterization in Nichols and Dyer's 1977 study of 4-substituted mescaline analogssupported
Replacement of the 4-methoxy of mescaline with higher alkyl homologues or with bromine led to increased activity at serotonin receptors in a sheep umbilical artery preparation. pmid:836502
The compound's primary research significance lies in its role as a reference point for structure–activity studies of phenethylamine psychedelics.supported
Escaline (compound 70) is psychoactive. Fluoroescaline (76) almost devoid of psychoactivity; difluoroescaline (77) retained escaline potency; trifluoroescaline (78) showed increased human potency vs escaline. dta.413
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
This mechanism is confirmed by ketanserin blockade of mescaline's psychedelic effects in controlled human trialssupported
Ketanserin attenuated effects confirming 5-HT2A as primary mechanism. s41398-024-03116-2
In murine head-twitch response assays, escaline produces 5-HT₂A-mediated behavioral responses with greater potency than mescaline.supported
Homologation of 4-methoxy to ethoxy (escaline) or propoxy (proscaline) increased potency in HTR. 0269881119826610
Cardiovascular stimulation — tachycardia documented by Shulgin, with dose-dependent blood pressure elevation expected from mescaline data — is the primary acute physiological concernsupported
Increased blood pressure and heart rate. s41398-024-03116-2
Rapid tolerance develops through 5-HT₂A receptor downregulation in the frontal cortex, with cross-tolerance expected to lsd, psilocybin, and mescalinesupported
Tolerance via 5-HT2A receptor downregulation in frontal cortex. Cross-tolerance between DOI and LSD. acschemneuro.2c00170
Rapid tolerance develops through 5-HT₂A receptor downregulation in the frontal cortex, with cross-tolerance expected to lsd, psilocybin, and mescalinesupported
Cross-tolerance among serotonergic hallucinogens. Evidence for therapeutic efficacy. j.bbr.2014.07.016
receptor-pharmacology8 · 6 ok
No potent affinity at dopamine receptors or monoamine transporters has been detectedsupported
No potent affinity at non-serotonergic targets. fphar.2021.794254
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
No TAAR1 activity has been reported for escaline; related scalines show weak to absent rat TAAR1 activity.supported
Scalines and 3C-scalines examined at serotonergic, adrenergic, dopaminergic, TAAR1, and monoamine transporter targets...No potent affinity at non-serotonergic targets. fphar.2021.794254
Parrish et al. (2005) demonstrated that phenethylamine 5-HT₂A agonists differ from their amphetamine analogs in phospholipase C activation profiles, indicating distinct downstream signaling properties between escaline and its α-methylated analog 3C-Esupported
Phenethylamines showed lower intrinsic activity than phenylisopropylamines. pmid:16277614
Nichols and Dyer (1977) demonstrated in a sheep umbilical artery serotonin receptor preparation that replacing mescaline's 4-methoxy group with higher alkyl homologues increases serotonin agonist activity, with potency correlating with lipophilicity measured by 1-octanol–water partition coefficientssupported
Replacement of the 4-methoxy of mescaline with higher alkyl homologues...led to increased activity at serotonin receptors in a sheep umbilical artery preparation. Activity correlated with lipophilicity (1-octanol-water partition coefficients). pmid:836502
Kolaczynska et al. (2021) confirmed that extending the 4-alkoxy substituent from methoxy to ethoxy increases both 5-HT₂A and 5-HT₂C binding affinities and enhances activation potency and efficacy at the 5-HT₂A receptorsupported
Extending 4-alkoxy substituent increases 5-HT2A/2C binding affinity. fphar.2021.794254
Fluorination of the 4-alkoxy group further amplifies this effectsupported
Trifluoroescaline (78) showed increased human potency vs escaline. dta.413
comparative-pharmacology5 · 5 ok
Activity peaks at intermediate chain lengths and diminishes when the substituent exceeds approximately five atomssupported
Activity drops off when 4-substituent is about five atoms in length. pmid:836502
The 43-fold improvement in 5-HT₂A binding affinity translates to a 5–8× increase in human psychoactive potency, consistent with typical phenethylamine affinity–potency relationshipssupported
Potency relationships closely parallel human hallucinogenic data. 0269881119826610
Parrish et al. (2005) demonstrated that phenethylamine 5-HT₂A agonists and their amphetamine analogs differ in phospholipase C activation profiles, indicating distinct downstream signaling despite targeting the same receptorsupported
Phenethylamines showed lower intrinsic activity than phenylisopropylamines. pmid:16277614
The scaline series — mescaline (methoxy), escaline (ethoxy), proscaline (propoxy), isoproscaline (isopropoxy), and higher homologues — demonstrates a systematic increase in 5-HT₂A/₂C affinity and psychoactive potency with extension of the 4-alkoxy chainpartially supported
Replacement of the 4-methoxy of mescaline with higher alkyl homologues...led to increased activity...Activity drops off when 4-substituent is about five atoms in length. pmid:836502
The scaline series — mescaline (methoxy), escaline (ethoxy), proscaline (propoxy), isoproscaline (isopropoxy), and higher homologues — demonstrates a systematic increase in 5-HT₂A/₂C affinity and psychoactive potency with extension of the 4-alkoxy chainsupported
Extending 4-alkoxy substituent increases 5-HT2A/2C binding affinity. fphar.2021.794254
neuroscience5 · 4 ok
Controlled trials of mescaline (500 mg) found subjective effects comparable to lsd (100 µg) and psilocybin (20 mg) on standardized measures of altered consciousness, suggesting equivalent engagement of these cortical circuits at equiactive dosessupported
No qualitative differences in altered states of consciousness at equipotent doses. s41386-023-01607-2
As a 5-HT₂A agonist with demonstrated behavioral activity in the head-twitch response assay, escaline is expected to affect brain systems through the same mechanisms established for other serotonergic psychedelics, though substance-specific confirmation is absent.supported
Homologation of 4-methoxy to ethoxy (escaline)...increased potency in HTR. Potency relationships closely parallel human hallucinogenic data. 0269881119826610
Claim in neuroscience — inconclusiveinconclusiveworking →
Tolerance to 5-HT₂A-mediated effects develops within 24 hours of a single administration via receptor downregulation in the frontal cortex — a process that does not require beta-arrestin-2 signalingpartially supported
Tolerance via 5-HT2A receptor downregulation in frontal cortex. Beta-arrestin-2 knockout does not prevent tolerance. acschemneuro.2c00170
What is escaline's receptor occupancy–subjective effect curve, and how does it compare to mescaline's dose-dependent altered consciousness profile established by Klaiber et al. (2024)?supported
Randomized, double-blind, placebo-controlled, crossover study; 16 healthy subjects; mescaline 100-800 mg...Dose-proportional PK. s41398-024-03116-2
clinical-evidence4 · 2 ok
Klaiber et al. (2024) conducted a double-blind, placebo-controlled, dose-response study of mescaline (100, 300, and 500 mg) in healthy subjects, reporting dose-dependent increases in altered states of consciousness, cardiovascular parameters (blood pressure, heart rate), and subjective drug effectssupported
Randomized, double-blind, placebo-controlled, crossover study; 16 healthy subjects; mescaline 100-800 mg...Dose-proportional PK...Increased blood pressure and heart rate. s41398-024-03116-2
Ley et al. (2023) compared mescaline (500 mg) head-to-head with lsd (100 µg) and psilocybin (20 mg) in a randomized, double-blind, placebo-controlled crossover trial in healthy participantssupported
RCT comparing mescaline (300/500 mg), LSD (100 ug), psilocybin (20 mg) in 32 healthy participants. s41386-023-01607-2
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Claim in clinical-evidence — inconclusiveinconclusiveworking →
chemistry2 · 2 ok
The scaline series — mescaline (methoxy), escaline (ethoxy), proscaline (propoxy), isoproscaline (isopropoxy), and higher homologues — represents a systematic exploration of how 4-alkoxy chain length modulates 5-HT₂A affinity and psychoactive potency.supported
Replacement of the 4-methoxy of mescaline with higher alkyl homologues...led to increased activity at serotonin receptors. Activity correlated with lipophilicity. pmid:836502
The scaline series — mescaline (methoxy), escaline (ethoxy), proscaline (propoxy), isoproscaline (isopropoxy), and higher homologues — represents a systematic exploration of how 4-alkoxy chain length modulates 5-HT₂A affinity and psychoactive potency.supported
Extending 4-alkoxy substituent increases 5-HT2A/2C binding affinity. fphar.2021.794254
history2 · 2 ok
The first systematic pharmacological characterization appeared in 1977, when Nichols and Dyer published a study in the Journal of Medicinal Chemistry demonstrating that replacing mescaline's 4-methoxy group with an ethoxy group increased serotonin receptor agonist activity in a sheep umbilical artery preparationsupported
Replacement of the 4-methoxy of mescaline with higher alkyl homologues or with bromine led to increased activity at serotonin receptors in a sheep umbilical artery preparation. pmid:836502
Trachsel's 2012 review of fluorinated psychedelic phenethylamines used escaline as a reference compound for psychoactive potency, situating it within the broader structure–activity landscape of the scaline series.supported
Escaline (compound 70) is psychoactive...Discusses comparative fluorinated SAR. dta.413
pharmacokinetic-detail2 · 0 ok
effects-overview1 · 0 ok
Claim in effects-overview — not_supportednot supportedworking →