generation run 2026-04-26
55 min completedmodel pipeline-v5plan not recordedrun/b13707b3…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
none raised on this run
Reproduce
- inputs
- 18 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
15 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | TMA-2 2,4,5-trimethoxyamphetamine pharmacology | 7 | 6 | All directly relevant to TMA-2 pharmacology, metabolism, and behavioral effects |
| 2 | PubChem | TMA-2 | 1 | 1 | Verified chemical identity data for TMA-2 |
| 3 | PubMed | TMA-2 trimethoxyamphetamine head twitch response hallucinogen potency | 2 | 0 | Duplicates of previously found articles |
| 4 | OpenAlex | TMA-2 trimethoxyamphetamine psychedelic | 10 | 3 | Relevant for pharmacology context, behavioral comparisons, and forensic detection |
| 5 | ClinicalTrials.gov · absence | TMA-2 trimethoxyamphetamine | 0 | 0 | No trials found |
| 6 | PsychonautWiki | TMA-2 dose duration history pharmacology | 1 | 0 | Confirmed existing dose/duration data, consistent with Shulgin PIHKAL |
| 7 | PubChem | TMA-2 CID 31014 | 1 | 1 | Verified chemical identity data for TMA-2 |
| 8 | PubMed | TMA drug discrimination DOM rat behavioral | 1 | 1 | Historical drug discrimination data for TMA series |
| 9 | Web - European Monitoring Centre | EMCDDA risk assessment TMA-2 2003 | 2 | 1 | Official EU drug risk assessment for TMA-2 |
| 10 | PubMed | 2,5-Dimethoxyamphetamine CYP2D6 metabolism TMA-2 | 2 | 2 | Key sources on TMA-2 metabolism and forensic detection |
| 11 | Web - DEA, EMCDDA, Canada CDSA | TMA-2 legal status scheduling | 5 | 3 | Primary legal sources for TMA-2 scheduling status |
| 12 | Web | TMA-2 Ki 5-HT2A binding affinity nM value receptor | 5 | 3 | Specific binding affinity data for TMA-2 |
| 13 | Web - DEA, Canada, UK | TMA-2 US DEA Schedule I status | 4 | 4 | Confirms legal status across major jurisdictions |
| 14 | Web | TMA-2 SMILES InChIKey CAS | 3 | 2 | Chemical structure data for TMA-2 |
| 15 | Web - Erowid/Historical sources | TMA-2 Shulgin history discovery 1962 1964 | 3 | 2 | Historical synthesis and discovery narrative |
47 claims by section — every cited sentence, checked against its source
safety11 · 7 ok
Tolerance develops rapidly — consistent with the well-characterized mechanism of 5-HT₂A receptor downregulation in the frontal cortexsupported
5-HT2A receptor downregulation (not 5-HT2C) is the mechanism of tolerance to hallucinogenic DOI; class-level mechanism relevant to TMA-2. pmid:10435391
Tolerance develops rapidly — consistent with the well-characterized mechanism of 5-HT₂A receptor downregulation in the frontal cortexsupported
5-HT2AR downregulation in frontal cortex. Tolerance mechanism independent of beta-arrestin-2. acschemneuro.2c00170
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Cross-tolerance with all classical serotonergic psychedelics — including LSD, psilocybin, mescaline, and other DOx compounds — is expected based on their shared 5-HT₂A mechanism.supported
Cross-tolerance between DOI and LSD. 5-HT2AR downregulation in frontal cortex. acschemneuro.2c00170
TMA-2's minimal monoamine transporter activity makes direct serotonin release amplification less likely than with MDMA or amphetaminesupported
Methoxylated phenethylamines (including TMA-2, 2C-I, 2C-E, 2C-C) had minimal effects on monoamine transport compared to stimulants. pmid:17223101
However, potent 5-HT₂A agonism could synergize with MAO inhibition to produce serotonergic toxicitysupported
Evaluates serotonin toxicity risks between serotonergic psychedelics and SSRIs/MAOIs. s00213-021-05876-x
Claim in safety — inconclusiveinconclusiveworking →
CYP2D6 substrates may be affected by TMA-2's competitive CYP2D6 inhibitionsupported
Interactions with CYP2D6 substrates are possible but unlikely at therapeutic concentrations. j.toxlet.2008.09.014
Concurrent MAOI use is contraindicated due to theoretical serotonin syndrome risk.supported
Evaluates serotonin toxicity risks between serotonergic psychedelics and SSRIs/MAOIs. s00213-021-05876-x
pharmacology10 · 5 ok
Claim in pharmacology — inconclusiveinconclusiveworking →
TMA-2 exerts its psychedelic effects primarily through agonism at the serotonin 5-HT₂A receptorsupported
Receptor binding affinities determined at 5-HT1A, 5-HT2A, 5-HT2C, TAAR1, alpha-adrenergic, D2 and monoamine transporters. Amphetamine derivatives Ki=61-4400 nM at 5-HT2A; preference over 5-HT1A and 5-HT2C. fphar.2019.01423
TMA-2 exerts its psychedelic effects primarily through agonism at the serotonin 5-HT₂A receptorsupported
TMA-2 at low doses increases locomotor activity in C57BL/6J mice. Effect mediated by 5-HT2A receptor activation. j.neuropharm.2013.01.014
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
TMA-2 exerts minimal influence on monoamine reuptake and release in rat brain synaptosomes, distinguishing it mechanistically from stimulant amphetamines such as amphetamine and MDMAsupported
TMA-2 and TMA-6 slightly influence reuptake and release of dopamine, 5-HT, and norepinephrine in rat brain synaptosomes. Methoxylated phenethylamines (including TMA-2, 2C-I, 2C-E, 2C-C) had minimal effects on monoamine transport compared to stimulants. pmid:17223101
Claim in pharmacology — inconclusiveinconclusiveworking →
CYP2D6 is the primary cytochrome P450 isoenzyme responsible for O-demethylation of TMA-2supported
CYP2D6 is the sole CYP isoenzyme involved in O-demethylation of TMA-2 and related compounds. j.toxlet.2008.09.014
TMA-2 acts as a non-mechanism-based competitive inhibitor of CYP2D6, with Ki values of 7.1–296 μM in recombinant CYP2D6 and 2.7–19.9 μM in pooled human liver microsomes — substantially weaker than potent CYP2D6 inhibitors such as quinidine (Ki = 0.0092 μM).supported
TMA-2 is a non-mechanism-based competitive inhibitor of CYP2D6 with Ki 7.1-296 microM (recombinant), 2.7-19.9 microM (HLM). j.toxlet.2008.09.014
Claim in pharmacology — not_supportednot supportedworking →
pharmacokinetic-detail7 · 6 ok
CYP2D6 is the principal cytochrome P450 isoform mediating O-demethylation of TMA-2supported
CYP2D6 is the sole CYP isoenzyme involved in O-demethylation of TMA-2 and related compounds. j.toxlet.2008.09.014
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
TMA-2 is a non-mechanism-based competitive inhibitor of CYP2D6:supported
TMA-2 is a non-mechanism-based competitive inhibitor of CYP2D6 with Ki 7.1-296 microM (recombinant), 2.7-19.9 microM (HLM). j.toxlet.2008.09.014
Standard ELISA immunoassay kits (amphetamine/MDMA panels) cannot reliably detect TMA-2 at concentrations up to 10,000 ng/mLsupported
Standard immunoassay kits cannot reliably detect TMA-2 and 29 other amphetamine designer drugs at concentrations up to 10,000 ng/mL. Specialized confirmatory methods required for forensic detection. bkw060
Definitive identification requires GC/MS or LC-MS/MS methodssupported
GC/MS STA procedure detects TMA-2 at common user doses in rat urine. pmid:16810708
Definitive identification requires GC/MS or LC-MS/MS methodssupported
Validated LC-MS method for simultaneous quantification of TMA, TMA-2, and TMA-6 in human urine. j.jchromb.2008.03.027
Comprehensive reviews of analytical approaches for 2,5-dimethoxyamphetamines in biological matrices are available.supported
Comprehensive review of analytical methods for DOx amphetamines and 2C-x phenethylamines in blood, urine, hair and other biological matrices. Reviews GC-MS and LC-MS methods. s11419-022-00638-6
comparative-pharmacology5 · 2 ok
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Unlike amphetamine and MDMA, TMA-2 produces minimal monoamine reuptake inhibition or release in rat brain synaptosomessupported
TMA-2 and TMA-6 slightly influence reuptake and release of dopamine, 5-HT, and norepinephrine in rat brain synaptosomes. Methoxylated phenethylamines (including TMA-2, 2C-I, 2C-E, 2C-C) had minimal effects on monoamine transport compared to stimulants. pmid:17223101
Drug discrimination studies in rats trained on DOM demonstrate cross-substitution with TMA isomers, with the 2,4-dimethoxy pattern identified as important for discriminative stimulus generalization within this classsupported
DOM-stimulus generalization in rat drug discrimination with TMA isomers. 2,4-dimethoxy pattern important for activity. pmid:6965276
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
receptor-pharmacology5 · 3 ok
All receptor data from Kolaczynska et al. (2019) unless otherwise notedsupported
Receptor binding affinities determined at 5-HT1A, 5-HT2A, 5-HT2C, TAAR1, alpha-adrenergic, D2 and monoamine transporters. fphar.2019.01423
Monoamine transporter data from Nagai et al. (2007).supported
TMA-2 and TMA-6 slightly influence reuptake and release of dopamine, 5-HT, and norepinephrine in rat brain synaptosomes. pmid:17223101
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Specific binding data at alpha-adrenergic and D₂ receptors for TMA-2 were not extractable from available published data, though the Kolaczynska et al. panel notes weak activity at non-5-HT₂ targets for the DO-OCH₃ (amphetamine series) compoundsupported
Receptor binding affinities determined at 5-HT1A, 5-HT2A, 5-HT2C, TAAR1, alpha-adrenergic, D2 and monoamine transporters. Amphetamine derivatives Ki=61-4400 nM at 5-HT2A; preference over 5-HT1A and 5-HT2C. fphar.2019.01423
summary4 · 1 ok
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
It is essentially inactive at 5-HT₁A (Ki ≈ 46,400 nM) and exerts minimal monoamine transporter activity, distinguishing it mechanistically from stimulant amphetamines.supported
Methoxylated phenethylamines (including TMA-2, 2C-I, 2C-E, 2C-C) had minimal effects on monoamine transport compared to stimulants. pmid:17223101
Claim in summary — inconclusiveinconclusiveworking →
neuroscience3 · 3 ok
The following mechanistic framework is inferred from the broader serotonergic psychedelic class and from TMA-2's confirmed 5-HT₂A agonism.supported
Receptor binding affinities determined at 5-HT1A, 5-HT2A, 5-HT2C, TAAR1, alpha-adrenergic, D2 and monoamine transporters. Amphetamine derivatives Ki=61-4400 nM at 5-HT2A; preference over 5-HT1A and 5-HT2C. fphar.2019.01423
The following mechanistic framework is inferred from the broader serotonergic psychedelic class and from TMA-2's confirmed 5-HT₂A agonism.supported
TMA-2 at low doses increases locomotor activity in C57BL/6J mice. Effect mediated by 5-HT2A receptor activation. j.neuropharm.2013.01.014
TMA-2's confirmed locomotor hyperactivity in mice, blocked by the selective 5-HT₂A antagonist M100907, confirms that its behavioral effects operate through the same 5-HT₂A-dependent pathwaypartially supported
TMA-2 at low doses increases locomotor activity in C57BL/6J mice. Effect mediated by 5-HT2A receptor activation. M100907 (5-HT2A antagonist) blocked the hyperactivity induced by mescaline and TCB-2. j.neuropharm.2013.01.014
chemistry1 · 1 ok
TMA-2 is the 4-methoxy member of the DOx series (also designated DO-OCH₃ or DOMeO), a family of 4-substituted 2,5-dimethoxyamphetamines within the broader class of substituted phenethylaminessupported
SAR context for the DOx class. Background: 2,4,5-Trimethoxyamphetamine (TMA-2) is a potent psychedelic compound. fphar.2019.01423
history1 · 0 ok
Claim in history — not_supportednot supportedworking →