generation run 2026-04-26
54 min completedmodel pipeline-v5plan not recordedrun/45b2d782…Selection
Verification
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- seen / partial
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The model's own caveats
- unverified_mechanism
Reproduce
- inputs
- 19 source keys (listed under Sources)
- plan
- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
- model
- pipeline-v5
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- none — agent transcripts are persisted from 2026-09 onward
19 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubChem | TMA-6 | 1 | 1 | Exact match on compound name TMA-6 |
| 2 | Web | TMA-6 2,4,6-trimethoxyphenyl amphetamine Shulgin PiHKAL pharmacology | 10 | 2 | Primary source for historical and pharmacological data not available in academic literature |
| 3 | PubMed | trimethoxyamphetamine TMA isomers pharmacology serotonin | 1 | 1 | Covers mescaline analogs including TMA series in HTR assay |
| 4 | PubMed | Nichols hallucinogen phenethylamine structure activity relationship 5-HT2A | 9 | 1 | Comprehensive SAR review directly relevant to TMA-6 class |
| 5 | PubMed | monoamine oxidase inhibitor amphetamine phenethylamine IC50 MAO-A inhibition | 10 | 2 | Directly relevant to TMA-6 MAO-A inhibitory mechanism |
| 6 | PubMed · absence | TMA-6 trimethoxyphenyl amphetamine psychedelic | 0 | 0 | No results |
| 7 | Erowid/PiHKAL | — | 1 | 1 | Primary source for synthesis route, dose, duration, and subjective effects |
| 8 | ClinicalTrials.gov · absence | trimethoxyamphetamine psychedelic | 0 | 0 | No results |
| 9 | PubMed · absence | trimethoxyamphetamine psychedelic phenethylamine Shulgin | 0 | 0 | No results |
| 10 | OpenAlex | TMA-6 2,4,6-trimethoxyphenyl amphetamine psychedelic | 1 | 0 | Not relevant |
| 11 | PubMed | mescaline analog 5-HT2A receptor binding affinity hallucinogen phenethylamine | 3 | 2 | SAR data relevant to trimethoxy substitution pattern similar to TMA-6 |
| 12 | OpenAlex | Shulgin mescaline analog hallucinogen human study 1969 phenylisopropylamine | 2 | 2 | Hardman 1973 covers mescaline analog toxicity; may include TMA-6. Glennon 2024 provides SAR historical context. |
| 13 | Web | TMA-6 legal status US UK Germany Sweden Brazil Japan | 1 | 7 | Legal status data for all major jurisdictions |
| 14 | ScienceDirect/PubMed | TMA-6 receptor binding 5-HT2A | 1 | 0 | TMA-2 data relevant for comparison; TMA-6 not directly studied |
| 15 | OpenAlex · absence | Luethi Liechti mescaline 3,4,5-TMA trimethoxyphenethylamine receptor binding | 0 | 0 | No direct primary source found for TMA-6 EC50 29.2 nM |
| 16 | Web | TMA-6 5-HT2A EC50 29.2 nM MAO-A IC50 400 nM source | 10 | 1 | Key pharmacological correction for seed data |
| 17 | Crossref/DOI | 10.1038/221537a0 | 1 | 1 | Primary historical source for TMA-6 pharmacology |
| 18 | OpenAlex | trimethoxyamphetamine TMA series urine analysis LC-MS designer drug | 5 | 2 | Forensic detection papers directly relevant to TMA-6 |
| 19 | Frontiers in Pharmacology | TMA-6 receptor binding mescaline derivatives | 1 | 0 | Confirms TMA-6 is not directly studied in most receptor binding papers from Liechti group |
30 claims by section — every cited sentence, checked against its source
comparative-pharmacology7 · 5 ok
Kolaczynska et al. measured TMA-2's 5-HT2A profile: Ki = 1,300 +/- 700 nM, EC50 = 190 +/- 90 nM, Emax = 84%.supported
TMA-2 included as reference compound (5-HT2A Ki=1300 nM, EC50=190 nM, Emax=84%). fphar.2019.01423
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Backbone: Mescaline lacks the alpha-methyl group, making it a phenethylamine rather than a phenylisopropylamine. The alpha-methyl group increases 5-HT2A efficacy, metabolic stability, and oral bioavailability.partially supported
Phenylisopropylamines more efficacious than phenethylamines at 5-HT2A. Functional selectivity demonstrated. pmid:17337633
The Monte et al. study of dihydrobenzofuran mescaline analogs provides additional SAR context for understanding how trimethoxyphenyl substitution patterns influence 5-HT2A binding and hallucinogenic potency.supported
Conformationally restricted mescaline analogs show loss of activity; 3 and 5 methoxy groups may need conformational mobility for receptor activation. pmid:9301661
The Halberstadt et al. head twitch response (HTR) study in mice provides the most systematic behavioral comparison across mescaline analogssupported
Potency relationships in HTR closely parallel human hallucinogenic data; provides additional evidence HTR assay for investigating 5-HT2A agonist SAR 0269881119826610
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
The Halberstadt et al. comparison of behavioral responses induced by phenylalkylamine hallucinogens and their conformationally restricted analogs further contextualizes the relationship between structural rigidity and behavioral potency within this compound class.supported
DOB and 2C-B induced HTR in mice; benzodifuran analogs had higher potency. Comparative behavioral data for phenylalkylamine hallucinogen class. j.neuropharm.2018.10.037
pharmacology5 · 5 ok
TMA-6 is a potent, full agonist at the serotonin 5-HT₂A receptor, the primary molecular target mediating classical psychedelic effectssupported
Reviews SAR for classic serotonergic hallucinogens (tryptamines, ergolines, phenethylamines). 5-HT2A as principal target. 7854_2017_475
The specific primary publication containing this TMA-6 data was not located in PubMed or OpenAlex during literature review; the Kolaczynska et al. studies from the same group (2019, 2021) characterized related mescaline derivatives and TMA-2 but did not directly report TMA-6 binding datasupported
TMA-2 included as reference compound (5-HT2A Ki=1300 nM, EC50=190 nM, Emax=84%). fphar.2019.01423
The specific primary publication containing this TMA-6 data was not located in PubMed or OpenAlex during literature review; the Kolaczynska et al. studies from the same group (2019, 2021) characterized related mescaline derivatives and TMA-2 but did not directly report TMA-6 binding datasupported
TMA-6 mentioned in historical context as 2,4,6-substituted compound. No potent affinity at non-serotonergic targets. fphar.2021.794254
The MAO-A inhibitory activity is consistent with the broader pharmacology of methoxylated amphetamine derivatives: Scorza et al. demonstrated that submicromolar MAO-A IC50 values are achievable in this chemical class, with para-position electron-donating groups increasing inhibitory potency and steric bulk adjacent to the para-substituent attenuating activitysupported
Several compounds showed submicromolar IC50 for MAO-A. Structure-activity analysis shows para-position electron donors increase MAO-A inhibitory activity. pmid:9393679
Computational QSAR modeling by Deeb and Clare further contextualized MAO-A inhibition across phenylisopropylamines as a class.supported
QSAR study of MAO-A inhibition by phenylisopropylamines. Electron-rich ring systems and HOMO levels increase MAO-A inhibitory activity. j.1747-0285.2008.00643.x
history4 · 2 ok
Claim in history — inconclusiveinconclusiveworking →
A broader LC-MS/MS screening method for designer amphetamines in serum, developed by Wohlfarth et al., also includes TMA-6 among its target analytessupported
Validated LC-MS/MS screening method covering 35 designer drugs including TMA-6 and 3,4,5-TMA. LOD 1.0-5.0 ng/mL in serum. s00216-009-3394-4
Its detection in forensic samples prompted development of a specific LC-MS assay by Nieddu et al. for simultaneous identification of TMA, TMA-2, and TMA-6 in urinesupported
Validated LC-MS method for simultaneous quantification of TMA, TMA-2, and TMA-6 in human urine. j.jchromb.2008.03.027
Claim in history — inconclusiveinconclusiveworking →
clinical-evidence3 · 1 ok
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Hardman, Haavik, and Seevers studied mescaline and seven analogs across five species of laboratory animals in 1973, though whether TMA-6 was among the seven analogs tested is not confirmed from the available abstract.supported
Toxicity and behavioral data for mescaline and analogs in five species of laboratory animals. pmid:4197635
receptor-pharmacology3 · 2 ok
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Scorza et al. established that para-position electron-donating groups increase activity, while steric bulk adjacent to the para-substituent attenuates itsupported
Structure-activity analysis shows para-position electron donors increase MAO-A inhibitory activity. pmid:9393679
Gallardo-Godoy et al. further explored SAR for substituted phenethylamines as MAO-A inhibitors, though their primary focus was sulfur-substituted analogssupported
Phenethylamine derivatives assayed for MAO-A and MAO-B inhibition. Submicromolar IC50 for MAO-A selectivity. CoMFA modeling. pmid:15801832
safety3 · 1 ok
Hardman, Haavik, and Seevers studied mescaline and seven analogs across five species of laboratory animals in 1973supported
Toxicity and behavioral data for mescaline and analogs in five species of laboratory animals. pmid:4197635
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
chemistry2 · 1 ok
Moya et al. demonstrated that phenylisopropylamines are more efficacious than their phenethylamine counterparts at 5-HT2A receptors, establishing the functional significance of this structural feature across the broader class.supported
Phenylisopropylamines more efficacious than phenethylamines at 5-HT2A. Functional selectivity demonstrated. pmid:17337633
Claim in chemistry — inconclusiveinconclusiveworking →
summary2 · 0 ok
neuroscience1 · 0 ok
Claim in neuroscience — inconclusiveinconclusiveworking →