αMT

# Research Output: ΑMT (alpha-methyltryptamine)

## Chemical Identity

**PubChem CID:** 9287 (verified via API) [Ref 17]

**Molecular formula:** C₁₁H₁₄N₂ (verified via PubChem) [Ref 17]

**Molecular weight:** 174.24 g/mol (verified via PubChem) [Ref 17]

**IUPAC name:** 1-(1H-indol-3-yl)propan-2-amine (verified via PubChem) [Ref 17]

**SMILES:** CC(N)CC1=CNC2=C1C=CC=C2 (verified via NCATS Inxight Drugs) [Ref 17]

**InChIKey:** QSQQQURBVYWZKJ-UHFFFAOYSA-N (verified via PubChem and NCATS) [Ref 17]

**CAS Number:** 299-26-3 (verified via NCATS Inxight Drugs) [Ref 17]

**FDA UNII:** BIK35ACJ0Q [Ref 17]

**Stereochemistry:** Racemic mixture (±); no published data establishing differential activity of enantiomers for AMT specifically. Close structural analog alpha-ethyltryptamine (AET) shows stereoselective activity: only S(+)-AET elicits weak partial 5-HT₂A agonist activity in calcium mobilization assays, though both enantiomers produce HTR in vivo (Silverman et al. 2025 [Ref 16]). AMT enantiomer-specific data absent from published literature.

**Seed data discrepancies:**
- The brief lists SMILES, molecular formula, molecular weight, InChIKey, and PubChem CID as blank. These have now been populated from verified sources. No contradictions found between seed data and published chemical identity — the systematic name (1-(1H-indol-3-yl)propan-2-amine) matches PubChem CID 9287.

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## Pharmacology

### Receptor Binding and Mechanism of Action

AMT has a multi-target pharmacological profile that underlies its combined stimulant and psychedelic character. Three primary mechanisms have been documented:

**1. Reversible MAO-A Inhibition**
AMT inhibits monoamine oxidase A (MAO-A) in a reversible manner. Wagmann et al. (2017 [Ref 4]) measured IC₅₀ values for AMT and 13 analogs against recombinant human MAO-A and MAO-B using an in vitro kynuramine assay. AMT showed MAO-A inhibition with IC₅₀ values in the range confirmed by the NCATS Inxight database (IC₅₀ 0.82 µM for MAO-A; IC₅₀ 60 µM for copper-containing amine oxidase/SSAO) [Ref 17]. AMT also inhibited MAO activity in human hepatic S9 fraction, indicating clinical relevance at physiological concentrations [Ref 4]. This MAO-A inhibition is a primary driver of drug-drug interaction risks (see Interactions section).

Renyi (1986 [Ref 15]) classified AMT explicitly as a "selective and reversible MAO-A inhibitor (as well as 5-HT releaser)" in a rat model, distinguishing it from irreversible MAO inhibitors. This dual characterization — both reversible MAOI and serotonin releaser — has been confirmed by subsequent literature.

The alpha-methyl substituent is mechanistically important: it reduces AMT's susceptibility to MAO-mediated degradation, thereby prolonging its half-life and allowing CNS penetration at lower doses than would be possible for non-methylated tryptamines [Ref 18].

**2. Monoamine Release (SERT, DAT, NET)**
AMT acts as a monoamine releasing agent, promoting efflux of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) from presynaptic terminals. NCATS Inxight reports "high affinity for the serotonin (5-HT) transporter" [Ref 17]. Li et al. (2025 [Ref 2]) demonstrated that AMT produces significant effects on DA, 5-HT and their metabolites (DOPAC, HVA, 5-HIAA) across rat brain regions (prefrontal cortex, nucleus accumbens, dorsolateral striatum, hippocampus), with dopaminergic and serotonergic systems both playing important roles.

Comparison with close structural analog alpha-ethyltryptamine (AET): Silverman et al. (2025 [Ref 16]) found that AET's behavioral effects rely on dual 5-HT₂A direct agonism AND indirect serotonergic potentiation via SERT-mediated serotonin release (fluoxetine pretreatment abolished AET-induced HTR). By structural and mechanistic analogy, AMT is expected to share this dual mechanism. This distinguishes AMT from classical psychedelics (which act mainly via direct 5-HT₂A agonism) and places it in a unique pharmacological niche.

**3. 5-HT₂A Receptor Agonism**
Li et al. (2025 [Ref 1]) demonstrated that AMT induces head-twitch response (HTR) in mice, which was completely blocked by the selective 5-HT₂A antagonist M100907 (0.01 mg/kg). This confirms that AMT's hallucinogenic-like effects are mediated via 5-HT₂A receptor activation, consistent with the established pharmacology of psychedelic tryptamines reviewed by Araújo et al. (2015 [Ref 7]) and Luethi & Liechti (2020 [Ref 10]).

**Quantitative receptor data:** No published Ki or EC₅₀ values at the 5-HT₂A receptor are available for AMT specifically. Published Ki values exist for structural analogs but cannot be reliably extrapolated to AMT without primary data. This is a gap. ⚑ FLAG FOR HUMAN REVIEW.

**Pharmacokinetic data:** No published human pharmacokinetic studies exist for AMT. Bioavailability, Tmax, and plasma half-life have not been formally characterized. The prolonged duration (13–15 hours total per clinical and user reports) is consistent with the combined effects of MAO-A inhibition (reducing 5-HT degradation) and the alpha-methyl group reducing MAO-mediated metabolism of AMT itself.

### Metabolism

Malaca et al. (2023 [Ref 22]) conducted the first comprehensive AMT metabolism study in humans using pooled human hepatocyte incubations and postmortem biological samples from an AMT overdose case. Nine metabolites were identified in vitro; eight additional metabolites were found in urine; five metabolites were found in blood. Metabolic transformations included:
- Hydroxylation
- O-sulfation
- O-glucuronidation
- N-glucuronidation
- N-acetylation

These are consistent with the metabolism of structural tryptamine analogues. Recommended biomarkers for AMT detection:
- **Urine (non-hydrolyzed):** α-MT, hydroxy-α-MT glucuronide, two hydroxy-α-MT sulfate isomers
- **Blood:** α-MT, two hydroxy-α-MT sulfate isomers, N-acetyl-α-MT

No specific CYP enzyme isoform involvement has been published for AMT. By class analogy with other tryptamines and indolealkylamines, CYP2D6 and CYP3A4 are likely candidates, but substance-specific data are absent. ⚑ FLAG FOR HUMAN REVIEW.

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## History

### Discovery and Synthesis

Alpha-methyltryptamine was first synthesized in the early 1960s simultaneously by Upjohn Pharmaceuticals (US, code U-14,164E) and Sandoz Pharmaceuticals (code IT-290), both investigating monoamine oxidase inhibitors as potential antidepressants [Refs 6, 17, 18]. The compound's antidepressant activity was attributed to its reversible MAO-A inhibitory action.

AMT was marketed commercially in the Soviet Union under the brand name **Indopan** (also spelled "Indopane"), available as 5 mg and 10 mg oral tablets, as a treatment for depression and bipolar disorder [Ref 17, Ref 18]. The drug was eventually withdrawn from production due to serious side effects, the specific nature of which are not detailed in English-language published literature. ⚑ FLAG: Specific clinical reasons for Soviet withdrawal not documented in accessible sources.

### Recreational Re-emergence

Following its pharmaceutical discontinuation, AMT re-emerged as a recreational "research chemical" in the late 1990s and early 2000s, distributed via the internet and marketed as a legal alternative to controlled psychedelics [Refs 7, 9]. Its popularity was amplified by online discussion communities and vendor availability before scheduling occurred.

The first documented AMT-related death in the United States occurred in February 2003 in Miami-Dade County (Boland et al. 2005 [Ref 6]), which directly triggered emergency DEA scheduling. AMT first appeared in the UK drug market in February 2011 [Ref 18].

Deaths and serious intoxications related to AMT have been reported in the United States, United Kingdom, Sweden, Norway, and Japan [Ref 26].

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## Subjective Effects

No controlled human studies describing AMT's subjective effects have been published. The following characterization is drawn from clinical toxicology case series and harm reduction sources; these should be labeled accordingly in any generated article.

**Stimulant effects** (consistent with monoamine release mechanism):
- Increased energy and wakefulness
- Appetite suppression
- Elevated heart rate and cardiovascular stimulation
- Elevated mood, empathy enhancement
- Cognitive acceleration

**Psychedelic effects** (consistent with 5-HT₂A agonism):
- Visual hallucinations including patterning, drifting, tracers, afterimages
- Color enhancement and alteration
- Internal hallucinations (closed-eye visuals)
- Music enhancement
- Altered time perception
- Conceptual thinking and thought connectivity

**Negative/adverse effects** (documented in UK NPIS data and harm reduction sources):
- Nausea and vomiting (common, especially at onset)
- Headache
- Anxiety, agitation, paranoia
- Blurred vision
- Incoordination
- Excessive sweating
- Temperature dysregulation
- Hyperreflexia
- Prolonged insomnia (consistent with 13–15 hour duration)
- Stimulant-type comedown: low mood, flu-like symptoms 1–2 days after use

Kamour et al. (2014 [Ref 5]) reported on UK NPIS cases, characterizing clinical presentation patterns after AMT use. Li et al. (2025 [Refs 1, 2]) characterized AMT's hallucinogenic-like behavior in mice as inhibiting locomotor activity (despite stimulant properties) and inducing HTR, suggesting a complex dose-dependent behavioral profile.

**Duration data:** The DB seed data (onset 60–180 min; peak 4–6 hours; aftereffects 1–5 hours; total 13–15 hours) is consistent with:
- Clinical reports noting delayed onset and prolonged duration
- DrugWise factsheet guidance emphasizing "always start low and slow" given slow onset [Ref 18]
- The mechanism of action (MAO-A inhibition reduces serotonin degradation, extending effects)
No controlled studies have formally characterized dose-duration relationships in humans.

**Dose data:** The DB seed data (threshold 5 mg; light 10–25 mg; common 25–40 mg; strong 40–60 mg; heavy 60+ mg; all oral) is consistent with published community consensus and the Boland et al. (2005 [Ref 6]) case report context (victim had 1 g vial of AMT, gastric content of 9.6 mg total at autopsy — suggesting dose in the common-to-heavy range was ingested). No controlled dose-response studies in humans. ⚑ FLAG: Dose ranges are based on community consensus, not controlled studies.

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## Safety & Toxicity

### LD50 and Lethal Dose

No formal LD50 data have been published for AMT in any species. Li et al. (2025 [Ref 1]) confirmed acute toxic effects in mice at experimental doses, consistent with the seed data noting "toxic dose is unknown." The DB seed data reflects this accurately.

**Postmortem concentration data from fatal cases:**
- Boland et al. (2005 [Ref 6]): First US death — postmortem iliac vein blood: **2.0 mg/L**; liver: 24.7 mg/kg; brain: 7.8 mg/kg; gastric contents: 9.6 mg total AMT; additional non-fatal antemortem serum: 1.5 mg/L
- Epain et al. (2024 [Ref 3]): Fatal co-intoxication — postmortem peripheral blood: **4,690 ng/mL (4.69 mg/L)** of AMT combined with 5-MAPB (101 ng/mL), benzodiazepines, ephedrine, norephedrine

The wide range in blood concentrations between these fatal cases (2.0 vs. 4.69 mg/L) and the polydrug context of the 2024 case make it difficult to establish a lethal threshold. ⚑ FLAG FOR HUMAN REVIEW: Lethal blood concentration range unconfirmed; polydrug contexts complicate interpretation.

### Clinical Toxicity Profile

Kamour et al. (2014 [Ref 5]) documented AMT toxicity patterns from UK NPIS reports. The Schifano et al. (2021 [Ref 8]) systematic review confirmed AMT's implication in serotonin syndrome cases, characterized by the classic triad: altered mental status, neuromuscular effects, autonomic hyperactivity.

Documented clinical manifestations of AMT toxicity:
- **Cardiovascular:** Tachycardia, hypertension
- **Neurological:** Hyperreflexia, clonus, tremor, agitation, confusion, seizures
- **Autonomic:** Hyperthermia, diaphoresis (excessive sweating), mydriasis
- **Metabolic:** Rhabdomyolysis (with potential acute kidney injury)
- **Psychiatric:** Paranoia, psychosis at high doses

DrugWise UK [Ref 18] specifically documents hyperthermia, hyperreflexia, clonus, hypertension, mydriasis, and rhabdomyolysis as serotonin toxicity manifestations.

### Organ Toxicity

No published organ-specific toxicology studies for AMT. Rhabdomyolysis (muscle breakdown) documented in clinical cases suggests potential renal toxicity secondary to myoglobinuria. No hepatotoxicity, cardiotoxicity, or neurotoxicity data specific to AMT from controlled studies.

### Psychological Risks

Risk of acute anxiety, panic attacks, and paranoia documented in clinical case series. Duration-related psychological distress is common given the 13–15 hour total duration and the prolonged stimulant-phase insomnia. Hallucinogen Persisting Perception Disorder (HPPD) risk has not been formally studied for AMT specifically but is plausible given 5-HT₂A agonism (class effect).

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## Harm Reduction

### Published Risk Reduction Guidance

Based on the clinical evidence assembled:

1. **Start very low due to slow onset:** The 60–180 minute oral onset creates significant redosing risk if users assume insufficient effect. DrugWise [Ref 18] and clinical toxicology data (Boland 2005 [Ref 6]) confirm this is a primary overdose risk factor.

2. **Avoid all serotonergic combinations:** AMT is both a MAO-A inhibitor and serotonin releaser. Combining with SSRIs, SNRIs, MAOIs, MDMA, tramadol, dextromethorphan, lithium, or other serotonergic substances creates serious serotonin syndrome risk [Refs 4, 8, 25]. Schifano et al. (2021 [Ref 8]) specifically implicated AMT in serotonin syndrome cases.

3. **Avoid stimulant combinations:** Cocaine and other stimulants combined with AMT create cardiovascular risk and augment hyperthermia risk.

4. **Avoid dissociative combinations:** PCP, rolicyclidine, MXE, and DXM combinations listed as lethal in the seed data are plausible given the serotonergic and cardiovascular mechanisms.

5. **Never combine with opioids:** Tramadol has serotonergic activity and is listed as lethal in combination with AMT in the seed database.

6. **Set and setting:** Given the prolonged 13–15 hour duration, AMT use should not be undertaken without planning for a full day-plus recovery window.

7. **Testing:** AMT cross-reacts with amphetamine immunoassays (confirmed by Boland 2005 [Ref 6]). Reagent testing (e.g., Marquis reagent — orange/brown for tryptamines) and fentanyl test strips recommended.

### Emergency Response

Suspected serotonin syndrome: remove physical stimulation, ensure cooling for hyperthermia, benzodiazepines for neuromuscular agitation, avoid antipsychotics (risk of lowering seizure threshold), seek emergency medical care. Cyproheptadine (5-HT₂A antagonist) has been used in serotonin syndrome management.

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## Tolerance & Dependence

### Tolerance

AMT produces rapid tolerance consistent with its 5-HT₂A agonist component. de la Fuente Revenga et al. (2022 [Ref 23]) demonstrated that a single administration of psychedelic 5-HT₂A agonists induces tolerance to subsequent doses within 24 hours, via 5-HT₂A receptor downregulation in the frontal cortex. This is the mechanism underlying the seed data's claim that tolerance builds "almost immediately after ingestion."

The seed data specifies: tolerance half-life 14 days; full reset 1 month. These values are consistent with published community consensus for psychedelic class tolerance and are mechanistically plausible given the timescale of receptor re-expression, but no AMT-specific published study confirms these exact durations.

### Cross-Tolerance

Cross-tolerance with other psychedelics (psilocybin, LSD, DMT, mescaline) is expected based on shared 5-HT₂A receptor downregulation mechanism (de la Fuente Revenga et al. 2022 [Ref 23]). The seed data's "cross-tolerances: psychedelics" is supported by this literature.

### Dependence Liability

5-MeO-AMT (closely related analog) showed no conditioned place preference, locomotor sensitization, or self-administration in mice, suggesting low reward/reinforcement profile (Abiero et al. 2019 [Ref 24]). By structural analogy, AMT is expected to have low classical addiction potential, consistent with the broader psychedelic class. The seed data's characterization of AMT as "moderately habit-forming" may reflect its stimulant component (dopamine/norepinephrine release) rather than compulsive use drive. No published dependence studies specific to AMT exist.

⚑ FLAG FOR HUMAN REVIEW: "Moderately habit-forming" characterization in seed data is not confirmed by published primary research for AMT. May be inferred from stimulant mechanism. Structural analog 5-MeO-AMT shows low abuse potential in animal models.

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## Interactions

The seed data lists the following interaction severities. The pharmacological basis for each is established here:

**Lethal Interactions (seed data):**
- **MDMA:** Both AMT (MAOI + serotonin releaser) and MDMA (SERT substrate/serotonin releaser) cause massive serotonin efflux. Combined action creates extreme serotonin syndrome risk. Confirmed dangerous by mechanistic evidence [Refs 4, 8, 25].
- **Tramadol:** Tramadol has serotonergic activity (SERT inhibition, mild MAOI); combining with a MAOI is a well-established dangerous interaction documented across clinical literature [Ref 25].
- **Dextromethorphan (DXM):** DXM inhibits SERT and has weak MAOI activity; combination with AMT's MAOI creates serotonin syndrome risk [Ref 25].
- **Cocaine:** Dopamine/NE reuptake inhibitor + monoamine releaser creates cardiovascular and serotonergic toxicity.
- **PCP / Rolicyclidine / Methoxetamine:** Dissociatives combined with serotonergic agents can cause unpredictable behavioral toxicity; mechanistic basis for "lethal" severity not fully documented in published literature. ⚑ FLAG FOR HUMAN REVIEW.
- **Mescaline:** Both are serotonergic; combination increases 5-HT₂A stimulation risk. ⚑ FLAG: "Lethal" severity not specifically documented in published literature for this combination.

**Unknown Interactions (seed data):**
- Cannabis, Alcohol, Caffeine: No published human data on these interactions with AMT specifically. Cannabis may augment anxiety/paranoia at high doses; alcohol may potentiate impairment and dehydration during a prolonged 13-15 hour experience.

The Wagmann et al. (2017 [Ref 4]) MAO-A IC₅₀ data is the key published basis for understanding the drug interaction profile: AMT inhibits MAO-A at clinically relevant concentrations, making it dangerous with all MAO-A substrates that depend on this enzyme for breakdown.

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## Legal Status

### United States
- **Temporary Schedule I:** April 4, 2003 (Federal Register [Ref 13]) — triggered by the first US fatal case (Boland et al. 2005 [Ref 6]) in February 2003
- **Permanent Schedule I:** September 29, 2004 (Federal Register [Ref 14]) — based on DHHS recommendation and DEA review; AMT found to meet all Schedule I criteria
- DEA street name: "Spirals"

### United Kingdom
- **Class A drug** effective January 7, 2015 — following ACMD (Advisory Council on the Misuse of Drugs) recommendation [Ref 18, Ref 26]
- Penalties: possession up to 7 years imprisonment and/or unlimited fine; supply up to life imprisonment and/or unlimited fine
- Prior to 2015, AMT was marketed as a "legal high" and first appeared in the UK in February 2011 [Ref 18]

### Other Jurisdictions
- **Australia:** Schedule 8 (controlled drug) [Ref 26]
- **Germany:** Controlled under the Narcotics Act (Betäubungsmittelgesetz, BtMG) [Ref 26]
- **Japan:** Controlled substance [Ref 26]
- **Canada:** Not explicitly nor implicitly controlled as of 2025 [Ref 26] ⚑ FLAG FOR HUMAN REVIEW: Canadian status should be verified against current Health Canada scheduling

### International
No UN Convention scheduling of AMT has been found. However, WHO Expert Committee on Drug Dependence (ECDD) has conducted a review (a PDF document was located but could not be extracted). ⚑ FLAG: WHO ECDD review document exists but content could not be retrieved programmatically.

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## Clinical Trials

No clinical trials involving alpha-methyltryptamine as an active intervention have been identified on ClinicalTrials.gov. A historical reference to NCT04053582 in a third-party database (NCATS) was investigated and confirmed to be unrelated to AMT (it is a mindfulness training study). AMT has no current or planned clinical development.

The compound's historical pharmaceutical development (Upjohn/Sandoz 1960s; Soviet Indopan) was pre-dating modern clinical trial registration requirements; no published clinical trial data from that era was retrieved in English-language databases.

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## Community Feedback Analysis

No community feedback was submitted in Part A2 of the brief. This section is therefore not applicable.

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## Gaps & Flags

### Data Absent from Published Literature

1. **No human pharmacokinetic study:** Bioavailability, Tmax, plasma half-life, volume of distribution — none published. Duration data relies on clinical reports and community consensus.

2. **No published Ki or EC₅₀ at 5-HT₂A receptor for AMT specifically:** 5-HT₂A agonism is confirmed behaviorally (HTR blocked by M100907) but quantitative binding affinity data are absent.

3. **No published CYP enzyme specifics for AMT:** Metabolism (hydroxylation, conjugation pathways) documented by Malaca et al. 2023 [Ref 22] but CYP isoform contributions not characterized.

4. **No formal LD50 in any species:** Acute toxic effects confirmed in mice (Li et al. 2025 [Ref 1]) but LD50 not established.

5. **Specific reasons for Soviet pharmaceutical withdrawal:** Not documented in accessible English-language literature.

6. **No stereochemistry study for AMT specifically:** Racemate is used recreationally; differential enantiomer activity unstudied (only AET studied, Silverman et al. 2025 [Ref 16]).

7. **Dependent/withdrawal characterization:** No published withdrawal syndrome description for AMT.

### Safety-Critical Values Not Confirmed by Published Sources

- **"Lethal" severity for PCP, Rolicyclidine, MXE, and Mescaline combinations:** Plausible mechanistically but not documented in published case reports specifically. ⚑ FLAG FOR HUMAN REVIEW.
- **Lethal blood concentration threshold:** Two fatal cases (2.0 mg/L and 4.69 mg/L in polydrug context) provide reference points but not a confirmed threshold. ⚑ FLAG FOR HUMAN REVIEW.
- **"Moderately habit-forming" dependence characterization:** Not confirmed by substance-specific published research. Low abuse potential shown for structural analog 5-MeO-AMT. ⚑ FLAG FOR HUMAN REVIEW.

### Contradictions Between Seed Data and Published Sources

- **PubChem CID missing in seed data:** CID is 9287 — now confirmed.
- **SMILES, formula, weight, InChIKey missing in seed data:** All now confirmed from PubChem and NCATS.
- No direct contradictions found between seed pharmacological class data and the published literature; the triple classification (MAOI + monoamine releasing agent + 5-HT₂A agonist) is strongly supported.

### Sections Relying Primarily on Structural Analogy

- MAO-A inhibition is **substance-specific** (Wagmann et al. 2017 [Ref 4]; NCATS IC₅₀ 0.82 µM [Ref 17])
- 5-HT₂A agonism is **substance-specific** (Li et al. 2025 [Ref 1]; HTR mouse data)
- Monoamine release: partially **analog-inferred** from AET studies (Silverman et al. 2025 [Ref 16]) and rat neurotransmitter data (Li et al. 2025 [Ref 2])
- CYP enzyme involvement: entirely **class inference** — no AMT-specific data
- Dependence characterization: partially **analog-inferred** from 5-MeO-AMT (Abiero et al. 2019 [Ref 24])
- Tolerance half-life and reset durations: **community consensus** without published AMT-specific studies