generation run 2026-05-11
72 min completedmodel pipeline-v5plan not recordedrun/c974ce21…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
5 further caveats recorded as free text — readable on the working page
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
17 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | 2C-T phenethylamine psychedelic thio substituent serotonin receptor | 1 | 1 | Directly studies the 2C-T subclass to which 2C-T-21 belongs; uses HTR as psychedelic activity proxy |
| 2 | PubMed · absence | 2C-T-21 psychedelic phenethylamine | 0 | 0 | Null result indicates sparse published data; must rely on class-level and analog literature |
| 3 | ClinicalTrials.gov · absence | 2C-T-21 phenethylamine psychedelic | 0 | 0 | Confirms no clinical trial activity for this compound |
| 4 | OpenAlex | 4-thio-substituted 2,5-dimethoxyphenethylamine structure activity relationship psychedelic | 10 | 5 | All relevant to 2C-T class pharmacology, toxicology, and SAR; provide class-level data applicable to 2C-T-21 |
| 5 | PubChem | 2C-T-21 | 1 | 1 | Primary chemical identity data for 2C-T-21; confirms seed data systematic name and adds formula, weight, InChIKey |
| 6 | PubMed | Wagmann 2C-T-7-FLY metabolism CYP isoenzyme MAO | 1 | 1 | Provides CYP enzyme and MAO involvement data for a closely related 2C-T-series compound |
| 7 | PubChem | 2C-T-21 CID 44349972 | 1 | 4 | Primary source for chemical identity data |
| 8 | PubMed | monoamine receptor interaction profiles 4-thio-substituted phenethylamines 2C-T drugs | 1 | 1 | Directly characterizes receptor binding for 2C-T series which includes or is closely related to 2C-T-21 |
| 9 | Web search | 2C-T-21 monoamine oxidase MAO inhibitor MAOI phenethylamine safety | 10 | 1 | Direct evidence of MAO inhibitory activity for 2C-T-21 from named compound testing |
| 10 | Web search | 2C-T-21 PIHKAL Shulgin fluoroethylthio synthesis | 10 | 3 | Primary historical source for 2C-T-21 discovery, dosing, and first human effect descriptions |
| 11 | PubMed Central | Halberstadt 2023 2C-T-21 full text PMC9816194 | 1 | 3 | Primary source for 2C-T-21 specific receptor binding and in vivo potency data |
| 12 | Web search | 2C-T-21 legal status scheduling DEA UK Canada Germany | 10 | 4 | Legal status information for major jurisdictions |
| 13 | Web search | Halberstadt 2023 4-thio 2C-T-21 fluoroethylthio head-twitch fourfold potency | 5 | 1 | Confirms critical SAR finding for 2C-T-21 |
| 14 | ClinicalTrials.gov · absence | 2C-T-21 phenethylamine psychedelic | 0 | 0 | Confirms complete absence of clinical trial activity |
| 15 | Erowid | PIHKAL entry #49 2C-T-21 | 1 | 3 | Primary source for historical dosing and effect descriptions |
| 16 | Web search | 2C-T-21 SMILES molecular structure ChemSpider fluoroethylthio | 10 | 2 | Chemical structure confirmation for SMILES field |
| 17 | OpenAlex | 2C-T-2 serotonin 5-HT2A receptor binding affinity Ki hallucinogen phenethylamine | 8 | 2 | Receptor pharmacology and cardiovascular safety context |
44 claims by section — every cited sentence, checked against its source
safety11 · 10 ok
Dean et al. documented at least five deaths attributed to 2C-series drugs, with excited delirium as a characteristic terminal presentation; sympathomimetic toxicity (tachycardia, hypertension, hyperthermia) and serotonin toxicity are the primary clinical syndromes observed in 2C intoxicationsupported
At least 5 deaths reported; excited delirium common among fatalities. Sympathomimetic and serotonin toxicity presentations. s13181-013-0295-x
Schifano et al. reported one death from mono-intoxication with the structurally analogous 2c-t-7 (propylthio vs. fluoroethylthio at C4) — the closest published precedent for lethal risk in the 2C-T subclass.supported
one death in USA from mono-intoxication documented pmid:16272191
Acute cardiovascular effects — blood pressure elevation and heart rate increase — have been documented in controlled human studies of the related compound 2c-b and are expected for 2C-T-21 based on serotonergic and sympathomimetic class pharmacology.supported
Increased BP and HR, euphoria, perceptual changes. fphar.2018.00206
Acute cardiovascular effects — blood pressure elevation and heart rate increase — have been documented in controlled human studies of the related compound 2c-b and are expected for 2C-T-21 based on serotonergic and sympathomimetic class pharmacology.supported
Acute sympathomimetic effects documented. s43440-023-00539-4
Claim in safety — inconclusiveinconclusiveworking →
MAO-A and MAO-B are the primary metabolic enzymes for the 2C-T series, so exogenous MAOI co-administration would impair 2C-T-21 clearance while simultaneously producing additive MAO inhibition from 2C-T-21's own inhibitory activitysupported
MAO-A and MAO-B are major enzymes in deamination. 2C compounds susceptible to drug-drug interactions with MAO inhibitors. j.bcp.2006.09.033
MAO-A and MAO-B are the primary metabolic enzymes for the 2C-T series, so exogenous MAOI co-administration would impair 2C-T-21 clearance while simultaneously producing additive MAO inhibition from 2C-T-21's own inhibitory activitysupported
2C-T-21 explicitly named. 13 showed MAO-A inhibition, 11 showed MAO-B inhibition. dta.2494
Chronic SSRI administration may also attenuate psychedelic effects through 5-HT₂A receptor downregulation.supported
Chronic SSRI/SNRI administration attenuates LSD effects in humans, attributed to 5-HT2A receptor downregulation. 0893-133x(95)00145-4
Cannabis may potentiate psychedelic intensity in a dose-dependent manner, increasing the probability of overwhelming or difficult experiences.supported
Cannabis combined with classic serotonergic psychedelics associated with more intense psychedelic experience (MEQ, ASC-Vis, EDI scores) in dose-dependent manner. s00213-021-05999-1
The dependence of 2C-T-21 metabolism on MAO enzymes combined with its own MAO inhibitory activity creates a pharmacokinetic-pharmacodynamic trap: the drug cannot be cleared while simultaneously amplifying monoaminergic activity.supported
MAO-A and MAO-B are major enzymes in deamination. 2C compounds susceptible to drug-drug interactions with MAO inhibitors. j.bcp.2006.09.033
The dependence of 2C-T-21 metabolism on MAO enzymes combined with its own MAO inhibitory activity creates a pharmacokinetic-pharmacodynamic trap: the drug cannot be cleared while simultaneously amplifying monoaminergic activity.supported
2C-T-21 explicitly named. 13 showed MAO-A inhibition, 11 showed MAO-B inhibition. MAO inhibition pharmacological contribution cannot be excluded. dta.2494
pharmacology10 · 7 ok
Claim in pharmacology — inconclusiveinconclusiveworking →
Halberstadt et al. reported a 5-HT₂A Ki of 27 nM for 2C-T-21, placing it within the 1–54 nM affinity range observed across the 2C-T seriessupported
5-HT2A Ki 1-54 nM j.neuropharm.2017.07.012
Claim in pharmacology — inconclusiveinconclusiveworking →
The absence of significant monoamine transporter activity (DAT/NET/SERT Ki > 4,000 nM across the 2C-T class) distinguishes this pharmacological profile from entactogen-class phenethylamines such as MDMA.supported
no monoamine transporter activity (Ki > 4000 nM) j.neuropharm.2017.07.012
Trace amine-associated receptor 1 (TAAR1) binding has been characterized for the 2C-T series as a class (Ki range 5–68 nM), though a discrete Ki value for 2C-T-21 specifically has not been publishedsupported
rat TAAR1 5-68 nM j.neuropharm.2017.07.012
Wagmann et al. demonstrated that 2C-T-21 inhibits both MAO-A and MAO-B in vitro, testing the compound directly among 12 2C-series substancessupported
2C-T-21 explicitly named. 13 showed MAO-A inhibition, 11 showed MAO-B inhibition. dta.2494
Claim in pharmacology — inconclusiveinconclusiveworking →
Theobald and Maurer identified MAO-A and MAO-B as the primary enzymes responsible for oxidative deamination of 2C-T-2 and 2C-T-7, converting the primary amine to the corresponding aldehyde; CYP2D6 contributes to a lesser extentsupported
MAO-A and MAO-B are major enzymes in deamination. CYP2D6 minor role for 2C-T-2 and 2C-T-7. j.bcp.2006.09.033
For the structurally related 2C-T-7-FLY, Wagmann et al. identified CYP2D6, CYP3A4, and FMO3 as phase I enzymes, with NAT1/NAT2 catalyzing N-acetylationsupported
Phase I: CYP2D6, 3A4, FMO3; N-acetylation by NAT1/NAT2. dta.2675
The dependence of 2C-T-21 metabolism on MAO enzymes has direct safety implications: concurrent administration of exogenous MAO inhibitors would substantially impair clearance, leading to elevated plasma concentrations and prolonged effects.supported
2C compounds susceptible to drug-drug interactions with MAO inhibitors. j.bcp.2006.09.033
comparative-pharmacology7 · 6 ok
It is the most extensively studied member of the 2C-T series, with one documented fatality from mono-intoxication and published in vitro neurotoxicity datapartially supported
one death in USA from mono-intoxication documented pmid:16272191
It is the most extensively studied member of the 2C-T series, with one documented fatality from mono-intoxication and published in vitro neurotoxicity datasupported
In vitro neurotoxicity study of 2C-T-2, 2C-T-4, 2C-T-7 and NBOMe counterparts in SH-SY5Y cells. jox14020044
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Despite this potency reduction, both compounds share a similar 5-HT₂A affinity range (2C-T-2 falls within the 1–54 nM class range)supported
5-HT2A Ki 1-54 nM j.neuropharm.2017.07.012
Both compounds share MAO-dependent primary metabolism and produce extended-duration psychedelic effects (2C-T-7: 8–15 hours; 2C-T-21: 7–12 hours)partially supported
MAO-A and MAO-B are major enzymes in deamination. j.bcp.2006.09.033
2c-b replaces the thioether entirely with a bromine atom at C4, producing a shorter-duration (4–6 hours), more dose-forgiving compound with controlled human pharmacological datapartially supported
Observational study of 2C-B (10, 15, 20 mg oral). Tmax of 2C-B ~1h. fphar.2018.00206
The thioether substituent also introduces MAO inhibitory activity absent in 2C-B, creating a dual-action pharmacological profile unique to the 2C-T subclass.supported
17 drugs tested (12 2Cs including 2C-T-21, plus 5 FLY analogs). 13 showed MAO-A inhibition, 11 showed MAO-B inhibition. dta.2494
summary7 · 6 ok
Halberstadt et al. reported compound-specific 5-HT₂A binding data (Ki = 27 nM) and in vivo head-twitch response potency in 2023, while Wagmann et al. confirmed direct MAO-A and MAO-B inhibitory activity in 2019partially supported
HTR dose-response studies with twelve different 4-thio-substituted phenylalkylamines conducted in male C57BL/6J mice. s00213-022-06279-2
Halberstadt et al. reported compound-specific 5-HT₂A binding data (Ki = 27 nM) and in vivo head-twitch response potency in 2023, while Wagmann et al. confirmed direct MAO-A and MAO-B inhibitory activity in 2019supported
17 drugs tested (12 2Cs including 2C-T-21, plus 5 FLY analogs). 2C-T-21 explicitly named. 13 showed MAO-A inhibition, 11 showed MAO-B inhibition. dta.2494
Claim in summary — inconclusiveinconclusiveworking →
The compound also inhibits MAO-A and MAO-B at micromolar concentrations — a dual property with significant drug interaction implications.supported
MAO-A IC50 10-125 µM (7 drugs); MAO-B IC50 1.7-180 µM (9 drugs). MAO inhibition pharmacological contribution cannot be excluded. dta.2494
No LD₅₀ or therapeutic index data exist for 2C-T-21; toxicity assessments derive entirely from structural analogy to the 2C-T class, where at least one fatality from 2c-t-7 and five class-level deaths have been documentedsupported
2C-T-7 market review; first synthesized 1986; one death in USA from mono-intoxication documented. pmid:16272191
No LD₅₀ or therapeutic index data exist for 2C-T-21; toxicity assessments derive entirely from structural analogy to the 2C-T class, where at least one fatality from 2c-t-7 and five class-level deaths have been documentedsupported
At least 5 deaths reported; excited delirium common among fatalities. s13181-013-0295-x
The confirmed MAO inhibitory activity creates a critical contraindication with exogenous MAO inhibitors and serotonergic medicationssupported
MAO inhibition pharmacological contribution cannot be excluded. dta.2494
receptor-pharmacology4 · 3 ok
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
The most detailed receptor interaction data for 2C-T-21 come from Halberstadt et al., who characterized 12 4-thio-substituted 2,5-dimethoxyphenylalkylamines using radioligand binding and functional assays.partially supported
HTR dose-response studies with twelve different 4-thio-substituted phenylalkylamines conducted in male C57BL/6J mice. s00213-022-06279-2
Luethi et al. characterized the broader 2C-T drug series, including compounds with fluoroethylthio substitution, providing class-level context for 2C-T-21:supported
Characterized monoamine receptor and transporter interaction profiles of 2C-T drug series including fluoroethylthio derivatives. j.neuropharm.2017.07.012
Wagmann et al. tested 2C-T-21 directly for monoamine oxidase inhibition, confirming activity at both MAO-A and MAO-Bsupported
2C-T-21 explicitly named. 13 showed MAO-A inhibition, 11 showed MAO-B inhibition. dta.2494
pharmacokinetic-detail3 · 3 ok
CYP2D6 contributes as a minor phase I pathwaysupported
CYP2D6 minor role for 2C-T-2 and 2C-T-7. j.bcp.2006.09.033
For the conformationally restricted analog 2C-T-7-FLY, Wagmann et al. identified additional phase I enzymes (CYP3A4, FMO3) and phase II N-acetylation via NAT1/NAT2supported
Phase I: CYP2D6, 3A4, FMO3; N-acetylation by NAT1/NAT2. dta.2675
A broader metabolic review by Meyer confirmed MAO and CYP involvement in 2C-T-2 and 2C-T-7 clearance.supported
Reviews metabolism of 2C compounds including 2C-T-2 and 2C-T-7. CYP and MAO isoenzyme-dependent metabolism. pmid:20540700
neuroscience2 · 1 ok
Claim in neuroscience — inconclusiveinconclusiveworking →
The additional MAO inhibitory activity of 2C-T-21 introduces a secondary monoaminergic modulation absent in classical psychedelics such as psilocybin or LSDsupported
2C-T-21 explicitly named. 13 showed MAO-A inhibition, 11 showed MAO-B inhibition. MAO inhibition pharmacological contribution cannot be excluded. dta.2494