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psx:substance/nm-2-ai/proposal/contraindication/1e0784e7-8705-4e71-bfcb-f9cca5b17487

proposal2026-05-11recordapproved

derived from · upstream

none recorded

feeds · downstream

Closure of psx:substance/nm-2-ai/proposal/contraindication/1e0784e7-8705-4e71-bfcb-f9cca5b17487: 0 upstream, 1 downstream.

psx:substance/nm-2-ai/proposal/contraindication/1e0784e7-8705-4e71-bfcb-f9cca5b17487
└─ derived_from  value/contraindication/19213cd5-61ff-473b-b3cd-998092a27a15@1

indented by distance from this node, not by parentage

1Provenance card

the boundary, as counts

Sources

2114 with DOI

1 strong · 16 moderate · 4 weak

Compilations

12026-05-11T06:34:48.178Z

pipeline-v5 · prompt hash not recorded — run predates 2026-09

Decisions

35last ruled 2026-10-02

0 awaiting a ruling

Issued documents

42026-10-02T13:09:45.072Z

notice · info card · emergency

Searches

191 with no results

queries and counts on the build

Claims checked

6959 supported

59 supported · 10 not

Correspondence

0received

consent field ships in Phase 4

Edges

230

derivations recorded for this entity

Complete over 21 sources, 1 compilation, and 35 decisions.Not here: the private journal (never).Working material — drafts, discards, unsupported claims — is listed below and readable on the working page.Cite: psychedex.org/substances/nm-2-ai/archive

2Build

one panel per compilation run

generation run 2026-05-11

60 min completedmodel pipeline-v5plan not recordedrun/1e06c7cd…

Selection

results seen99
selected by the model34
consumed as sources20

Verification

claims checked69
supported55
partially supported4
not supported3
inconclusive7
  • record
  • seen / partial
  • working

The model's own caveats

  • sparse_evidence
  • safety_data_unverified
  • structural_inference

Reproduce

inputs
20 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
19 searches — query, source, results, what was kept and why
19 searches for this run
#sourcequeryseenkeptrationale
1PubChemNM-2-AI / N-methyl-2-aminoindane11Core chemical identity confirmation for seed data verification
2PubMed2-aminoindane N-methyl pharmacology stimulant143Early aminoindane pharmacology papers and MDMA-analog drug discrimination studies provide mechanistic class context
3PubMedaminoindane new psychoactive substance forensic detection104NM2AI-specific metabolism data; MDAI human pharmacology as closest structural analog; forensic market data showing NM2AI in seized materials
4PubMedNM-2-AI aminoindane22Both directly about NM-2-AI; primary sources for toxicology and metabolism
5WebSearchNM-2-AI UK Psychoactive Substances Act scheduling US analog act102Jurisdiction-specific legal status
6PubChemCID 15023225 N-methyl-2-aminoindane11Chemical identity verification
7WebSearchNM-2-AI case report intoxication forensic death adverse event102Critical safety and forensic case data
8OpenAlexaminoindane monoamine releasing pharmacology new psychoactive substance102High-citation review papers providing context for aminoindane pharmacology class
9ClinicalTrials.gov · absenceaminoindane NM-2-AI 2-aminoindane0—No trials to report
10PubMedaminoindane MDAI monoamine transporter releasing agent SERT DAT NET11Key pharmacology data on aminoindane class NET/SERT/DAT selectivity
11UNODC—11International scheduling status
12PubMedNM2AI N-methyl aminoindane behavioral pharmacokinetics mice 202311Only direct in vivo behavioral/PK study of NM2AI
13PubMedHalberstadt 2-aminoindan ring-substituted monoamine transporters alpha2 adrenergic 201911Definitive pharmacology data on 2-AI and ring-substituted derivatives with Ki values
14WebSearchNM-2-AI N-methyl-2-aminoindane legal status scheduling UK US EU 2026103Legal status in key jurisdictions
15UNODC—12Chemical identity confirmation and CAS discrepancy flag
16WebFetch—12Key finding establishing research gap timeline
17WebSearchNM-2-AI case report intoxication forensic death adverse event102Forensic case documentation
18MultipleNM-2-AI pharmacological classification cross-reference52Critical pharmacological discrepancy needing expert editorial review
19WebSearchNM-2-AI pharmacology norepinephrine selective monoamine releasing transporter102Key pharmacological discrepancy requiring flagging
69 claims by section — every cited sentence, checked against its source
pharmacology17 · 15 ok
  • Simmler et al. (2014) characterized 2-AI at human monoamine transporters in HEK293 cells, demonstrating primary interaction with the norepinephrine transporter (NET) with substantially less involvement of the serotonin transporter (SERT) or dopamine transporter (DAT)supported

    2-AI interacted with NET. All substances were monoamine transporter inhibitors with marked differences in DAT vs SERT inhibition profiles. j.bcp.2014.01.024

  • Halberstadt et al. (2019) confirmed that 2-AI acts as a substrate for both NET and DAT, and further identified high-affinity binding at alpha-2 adrenergic receptor subtypes: alpha-2C (Ki = 41 nM), alpha-2A (Ki = 134 nM), and alpha-2B (Ki = 211 nM).supported

    2-AI is a substrate for NET and DAT. High alpha2C receptor affinity (Ki=41 nM), alpha2A (Ki=134 nM), alpha2B (Ki=211 nM). s00213-019-05207-1

  • Secondary sources describe NM-2-AI as a highly selective norepinephrine releasing agent that does not release serotonin or dopamine at concentrations up to 100 micromolar; however, this claim is not traceable to a specific primary publication and appears to derive from extrapolation of 2-AI data with the assumption that N-methylation enhances NET selectivitysupported

    2-AI interacted with NET. All substances were monoamine transporter inhibitors with marked differences in DAT vs SERT inhibition profiles. j.bcp.2014.01.024

  • Secondary sources describe NM-2-AI as a highly selective norepinephrine releasing agent that does not release serotonin or dopamine at concentrations up to 100 micromolar; however, this claim is not traceable to a specific primary publication and appears to derive from extrapolation of 2-AI data with the assumption that N-methylation enhances NET selectivitysupported

    2-AI is a substrate for NET and DAT. Ring substitution increases SERT selectivity. s00213-019-05207-1

  • Pinterova et al. (2017) explicitly noted that "there is currently no scientific information available about these compounds" regarding NM-2-AI.supported

    Specifically notes that as of 2017 'there is currently no scientific information available about NM-2-AI.' fpsyt.2017.00236

  • Little and Rees (1980) confirmed sympathomimetic properties for the N-methyl-2-aminoindane derivative in vitro on guinea-pig ileum, consistent with noradrenergic releasing activity.supported

    In vitro actions of 2-aminoindane and N-methyl/N,N-dimethyl derivatives on guinea-pig ileum. N-methyl derivative inhibited responses to electrical stimulation. Sympathomimetic properties. pmid:6110722

  • The parent 2-AI shows primary NET selectivity, unsubstituted aminoindanes favor NET/DAT over SERT as a structure-activity principle, and ring substitution (as in MDAI, MMAI) is required to shift selectivity toward serotonin releasesupported

    5-IAI and MDAI preferentially inhibited SERT and NET and released 5-HT. 2-AI interacted with NET. j.bcp.2014.01.024

  • The parent 2-AI shows primary NET selectivity, unsubstituted aminoindanes favor NET/DAT over SERT as a structure-activity principle, and ring substitution (as in MDAI, MMAI) is required to shift selectivity toward serotonin releasesupported

    2-AI is a substrate for NET and DAT. Ring substitution increases SERT selectivity. s00213-019-05207-1

  • Tirri et al. (2023) describe NM-2-AI as possessing "entactogenic activity" in mice, which may reflect in vivo serotonergic contributions not captured in vitro, activity of the 2-AI metabolite, or non-serotonergic mechanisms underlying the entactogenic phenomenologysupported

    Demonstrated entactogenic activity, mild hallucinogenic effect (PPI disruption). Main active metabolite is 2-aminoindane (2-AI). ijms24031882

  • Liechti (2015) notes that aminoindanes as a class "predominantly enhance serotonin release," but this characterization applies most strongly to ring-substituted compounds rather than unsubstituted or N-methyl analogs.supported

    Notes aminoindanes predominantly enhance serotonin release. smw.2015.14043

  • Claim in pharmacology — not_supportednot supportedworking →

  • The primary metabolic pathway is N-demethylation to 2-aminoindane (2-AI), which is itself pharmacologically active — Tirri et al. (2023) identify 2-AI as "the main active metabolite"supported

    Main active metabolite is 2-aminoindane (2-AI). ijms24031882

  • In pooled human liver microsomes (pHLM), NM-2-AI forms a hydroxylamine and diastereomers from beta-hydroxylationsupported

    NM-2-AI formed a hydroxylamine and diastereomers from beta-hydroxylation in pHLM. dta.2699

  • In rat urine, seven main metabolites were identified by LC-HRMS: 2-AI, two hydroxy-2-AI isomers, and four hydroxy-NM-2-AI isomers, with hydroxylated metabolites also present as sulfate conjugatespartially supported

    In silico and in vivo (mice) NM2AI metabolism study. Seven main metabolites in urine: 2-AI, two hydroxy-2-AI, four hydroxy-NM2AI; conjugation in some. bkaa111

  • The 2-AI metabolite undergoes acetyl conjugation via N-acetyltransferase isoform 2 (NAT2), which is polymorphically expressed in humans — slow acetylator phenotype individuals may experience prolonged exposure to active 2-AIsupported

    NAT acetylation isoform characterization. dta.2699

  • NM-2-AI and 2-AI were detected in hair and blood in mouse studiessupported

    NM2AI and 2-AI detected in hair and blood. bkaa111

  • Claim in pharmacology — inconclusiveinconclusiveworking →

safety13 · 13 ok
  • Jurowski and Frydrych (2026) published the first comprehensive toxicity profile of NM-2-AI using multiple computational platforms:supported

    This study provides the first toxicity profile of two aminoindane-based NPS: 2-AI and NM-2-AI, using a multi-method in silico approach. j.tiv.2025.106149

  • Predicted hERG inhibition IC50: 126.9 micromolar — suggesting low risk of QT prolongation at anticipated recreational concentrations, though this prediction has not been validated experimentally.supported

    hERG IC50 = 126.9 µM j.tiv.2025.106149

  • Skin irritation probability: 60%; eye irritation: predicted non-irritant.supported

    Skin irritation less probable (60%). Non-irritant to eye. j.tiv.2025.106149

  • MDAI provides the closest available experimental toxicology data for the aminoindane class: * LD50 in rats: 28.33 mg/kg subcutaneous, 35 mg/kg intravenous; not established up to 40 mg/kg oral * Cause of death: disseminated intravascular coagulopathy (DIC) with brain edema * Lethality at 100 mg/kg intraperitoneal in all 8 mice tested * Strong cytotoxic potential in human HepG2 hepatocyte cells, exceeding MDMA * Fatal human case: blood MDAI 2.09 mg/L (polydrug, alongside 5-EAPB 6.45 mg/L)supported

    MDAI LD50 = 28.33 mg/kg sc and 35 mg/kg iv in rats. Not established up to 40 mg/kg oral. Disseminated intravascular coagulopathy (DIC) with brain edema as cause of death. j.pnpbp.2016.04.004

  • MDAI provides the closest available experimental toxicology data for the aminoindane class: * LD50 in rats: 28.33 mg/kg subcutaneous, 35 mg/kg intravenous; not established up to 40 mg/kg oral * Cause of death: disseminated intravascular coagulopathy (DIC) with brain edema * Lethality at 100 mg/kg intraperitoneal in all 8 mice tested * Strong cytotoxic potential in human HepG2 hepatocyte cells, exceeding MDMA * Fatal human case: blood MDAI 2.09 mg/L (polydrug, alongside 5-EAPB 6.45 mg/L)supported

    MDAI LD50 = 28.33 mg/kg sc and 35 mg/kg iv in rats. Not established up to 40 mg/kg oral. Disseminated intravascular coagulopathy (DIC) with brain edema as cause of death. j.pnpbp.2016.04.004

  • MDAI provides the closest available experimental toxicology data for the aminoindane class: * LD50 in rats: 28.33 mg/kg subcutaneous, 35 mg/kg intravenous; not established up to 40 mg/kg oral * Cause of death: disseminated intravascular coagulopathy (DIC) with brain edema * Lethality at 100 mg/kg intraperitoneal in all 8 mice tested * Strong cytotoxic potential in human HepG2 hepatocyte cells, exceeding MDMA * Fatal human case: blood MDAI 2.09 mg/L (polydrug, alongside 5-EAPB 6.45 mg/L)supported

    Lethality in 8/8 mice at 100 mg/kg. fbp.0000000000000237

  • MDAI provides the closest available experimental toxicology data for the aminoindane class: * LD50 in rats: 28.33 mg/kg subcutaneous, 35 mg/kg intravenous; not established up to 40 mg/kg oral * Cause of death: disseminated intravascular coagulopathy (DIC) with brain edema * Lethality at 100 mg/kg intraperitoneal in all 8 mice tested * Strong cytotoxic potential in human HepG2 hepatocyte cells, exceeding MDMA * Fatal human case: blood MDAI 2.09 mg/L (polydrug, alongside 5-EAPB 6.45 mg/L)supported

    MDAI showed strong cytotoxic potential in HepG2 cells compared to moderate effects for MDMA and other NPS. j.toxlet.2018.11.007

  • MDAI provides the closest available experimental toxicology data for the aminoindane class: * LD50 in rats: 28.33 mg/kg subcutaneous, 35 mg/kg intravenous; not established up to 40 mg/kg oral * Cause of death: disseminated intravascular coagulopathy (DIC) with brain edema * Lethality at 100 mg/kg intraperitoneal in all 8 mice tested * Strong cytotoxic potential in human HepG2 hepatocyte cells, exceeding MDMA * Fatal human case: blood MDAI 2.09 mg/L (polydrug, alongside 5-EAPB 6.45 mg/L)supported

    Blood: MDAI 2.09 mg/L, 5-EAPB 6.45 mg/L. Cause of death attributed to NPS consumption. j.forsciint.2019.03.023

  • MDAI produced hyperthermia in group-housed rats (social conditions amplifying thermoregulatory disruption)supported

    Hyperthermia in group-housed rats. j.pnpbp.2016.04.004

  • Structural analog context: MDAI produced conditioned place preference in mice at 0.3–10 mg/kg, confirming abuse potential in the aminoindane classsupported

    Conditioned place preference 0.3-10 mg/kg. fbp.0000000000000237

  • Serotonin syndrome risk: Liechti (2015) notes that aminoindanes as a class are associated with acute serotonin syndrome risk at high doses or in combination with serotonergic agentssupported

    Reviews relative serotonergic vs dopaminergic activity as predictor of effects and toxicity. smw.2015.14043

  • Pharmacokinetic interactions: The NAT2 polymorphism affecting 2-AI acetylation introduces a variable: CYP inhibitors or NAT2 competitive substrates could prolong active metabolite exposuresupported

    NAT acetylation isoform characterization. dta.2699

  • Absolute contraindications (class-level inference): * Concurrent MAOI use: Risk of hypertensive crisis and serotonin syndrome * Uncontrolled hypertension: Noradrenergic activation elevates blood pressure; pre-existing hypertension compounds cardiovascular risk * Severe cardiovascular disease: Predicted 82% cardiovascular toxicity probability makes pre-existing cardiac pathology a high-risk factorsupported

    Cardiovascular toxicity probability 82% for NM-2-AI; hERG IC50 = 126.9 µM j.tiv.2025.106149

pharmacokinetic-detail8 · 5 ok
  • Manier et al. (2020) incubated NM-2-AI with pooled human liver microsomes (pHLM) and pooled human liver S9 fraction (pS9): * N-demethylation to 2-aminoindane (2-AI) — the primary metabolic pathway * Hydroxylamine formation — detected in both pHLM and pS9 * Beta-hydroxylation producing diastereomeric products (pHLM) * N-acetylation of the 2-AI metabolite via NAT2 (N-acetyltransferase isoform 2)supported

    NM-2-AI formed a hydroxylamine and diastereomers from beta-hydroxylation in pHLM. In pS9 merely a hydroxylamine. NAT acetylation isoform characterization. dta.2699

  • Mestria et al. (2021) characterized metabolites in rat urine following NM-2-AI administration, identifying seven main metabolites by LC-HRMS: * 2-AI (N-demethylation product) * Two hydroxy-2-AI isomers * Four hydroxy-NM-2-AI isomers * Sulfate conjugates of hydroxylated metabolitespartially supported

    In silico and in vivo (mice) NM2AI metabolism study. Seven main metabolites in urine: 2-AI, two hydroxy-2-AI, four hydroxy-NM2AI; conjugation in some. bkaa111

  • Both NM-2-AI and 2-AI were detected in mouse hair and blood samples, establishing relevance for forensic detection in chronic exposure scenarios.supported

    NM2AI and 2-AI detected in hair and blood. bkaa111

  • Tirri et al. (2023) confirmed 2-AI as "the main active metabolite" in their behavioral pharmacokinetic study in mice, establishing that the pharmacological activity of NM-2-AI in vivo is a composite of parent compound and active metabolite effects.supported

    Main active metabolite is 2-aminoindane (2-AI). Pharmacokinetics characterized. ijms24031882

  • Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →

  • Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →

  • Manier et al. (2020) and Mestria et al. (2021) developed validated LC-HRMS analytical methods for NM-2-AI and its metabolites in urine, blood, and hair matricessupported

    LC-HRMS method developed. bkaa111

  • Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →

comparative-pharmacology7 · 7 ok
  • MDAI at 180–228 mg produces subjective effects comparable to 125 mg MDMA in humans, with pronounced prosocial and empathogenic qualitiessupported

    MDAI produced effects comparable with 125 mg MDMA. Increased blood pressure similar to MDMA; no increase in heart rate or body temperature. dta.3622

  • MDAI carries established hepatotoxic risk (strong cytotoxic potential in HepG2 cells, exceeding MDMA) and a documented LD50 in rats (28.33 mg/kg subcutaneous)supported

    MDAI showed strong cytotoxic potential in HepG2 cells compared to moderate effects for MDMA and other NPS. j.toxlet.2018.11.007

  • MDAI carries established hepatotoxic risk (strong cytotoxic potential in HepG2 cells, exceeding MDMA) and a documented LD50 in rats (28.33 mg/kg subcutaneous)supported

    MDAI LD50 = 28.33 mg/kg sc and 35 mg/kg iv in rats. j.pnpbp.2016.04.004

  • Both are NET-preferring substrates with secondary DAT activity and minimal SERT involvementsupported

    2-AI interacted with NET. All substances were monoamine transporter inhibitors with marked differences in DAT vs SERT inhibition profiles. j.bcp.2014.01.024

  • Both are NET-preferring substrates with secondary DAT activity and minimal SERT involvementsupported

    2-AI is a substrate for NET and DAT. Ring substitution increases SERT selectivity. s00213-019-05207-1

  • N-methylation is expected to increase lipophilicity and CNS penetration (by analogy with amphetamine→methamphetamine), potentially explaining the lower dose threshold for NM-2-AI relative to 2-AI in community reports. 2-AI additionally shows high affinity at alpha-2 adrenergic receptors (Ki = 41 nM at alpha-2C); whether NM-2-AI retains this affinity is untested.supported

    High alpha2C receptor affinity (Ki=41 nM) s00213-019-05207-1

  • The 5-iodo substitution in 5-IAI shifts selectivity toward SERT similarly to MDAI, producing an entactogenic profile. 5-IAI shows preferential SERT and NET inhibition and 5-HT releasesupported

    5-IAI and MDAI preferentially inhibited SERT and NET and released 5-HT. j.bcp.2014.01.024

history7 · 6 ok
  • Claim in history — inconclusiveinconclusiveworking →

  • Little and Rees published one of the earliest in vitro characterizations of the 2-aminoindane series — including the N-methyl and N,N-dimethyl derivatives — in 1980, demonstrating sympathomimetic activity on guinea-pig ileum preparationssupported

    In vitro actions of 2-aminoindane and N-methyl/N,N-dimethyl derivatives on guinea-pig ileum. Sympathomimetic properties. pmid:6110722

  • Oberlender and Nichols (1990) demonstrated that N-methyl aminoindane derivatives retained MDMA-like discriminative stimulus properties in rats, while Johnson et al. (1991) confirmed that MDAI produced serotonin release without the neurotoxicity observed with MDMAsupported

    MDAI and its N-methyl derivative both showed entactogen-like MBDB-substitution, demonstrating that N-methylation of aminoindanes preserves entactogenic discriminative stimulus properties. pmid:1979813

  • Oberlender and Nichols (1990) demonstrated that N-methyl aminoindane derivatives retained MDMA-like discriminative stimulus properties in rats, while Johnson et al. (1991) confirmed that MDAI produced serotonin release without the neurotoxicity observed with MDMApartially supported

    MDAI studied as non-neurotoxic MDMA analogue. Combination of MDAI with S-amphetamine resulted in marked long-term decrease in cortical/hippocampal/striatal 5-HT, 5-HIAA, and 5-HT uptake sites. pmid:1726189

  • NM-2-AI emerged on the research chemical market as part of a broader wave of synthetic aminoindanes that appeared following the United Kingdom's ban on mephedrone and other synthetic cathinones in 2009–2010supported

    Aminoindanes emerged on market after UK cathinone bans in 2009-2010. fpsyt.2017.00236

  • NM-2-AI was seized and identified in Italian forensic laboratory materials during the 2013–2015 period, and Tirri et al. (2023) describe the compound as "briefly used in the illicit drug market".supported

    NM2AI (N-methyl-2-aminoindane) detected in seized materials in Italy 2013-2015. j.forsciint.2016.01.037

  • NM-2-AI was seized and identified in Italian forensic laboratory materials during the 2013–2015 period, and Tirri et al. (2023) describe the compound as "briefly used in the illicit drug market".supported

    Title: 'Behavioral and Pharmacokinetics Studies of N-Methyl-2-Aminoindane (NM2AI) in Mice: An Aminoindane Briefly Used in the Illicit Drug Market.' ijms24031882

summary6 · 5 ok
  • Claim in summary — inconclusiveinconclusiveworking →

  • NM-2-AI first appeared in the research chemical market circa 2009–2010 as part of a wave of aminoindane derivatives marketed as alternatives to banned cathinones and MDMAsupported

    Aminoindanes emerged on market after UK cathinone bans in 2009-2010. fpsyt.2017.00236

  • The sole direct behavioral study — conducted in mice — confirmed in vivo entactogenic activity and identified the N-demethylated metabolite 2-aminoindane as the primary active metabolitesupported

    First in vivo study of NM2AI in mice (IP 1-100 mg/kg). Demonstrated entactogenic activity. Main active metabolite is 2-aminoindane (2-AI). ijms24031882

  • The pharmacological mechanism is inferred primarily from the parent compound 2-aminoindane (2-AI), which acts as a substrate-type releaser at the norepinephrine transporter (NET) with secondary dopamine transporter (DAT) activity and minimal serotonin transporter (SERT) involvementsupported

    2-AI interacted with NET. All substances were monoamine transporter inhibitors with marked differences in DAT vs SERT inhibition profiles. j.bcp.2014.01.024

  • The pharmacological mechanism is inferred primarily from the parent compound 2-aminoindane (2-AI), which acts as a substrate-type releaser at the norepinephrine transporter (NET) with secondary dopamine transporter (DAT) activity and minimal serotonin transporter (SERT) involvementsupported

    2-AI is a substrate for NET and DAT. Ring substitution increases SERT selectivity. s00213-019-05207-1

  • In silico modeling predicts cardiovascular toxicity probability of 82% and elevated genotoxicity relative to the parent 2-AIpartially supported

    Cardiovascular toxicity probability 82% for NM-2-AI; genotoxicity probability 66.3% (Ames test). j.tiv.2025.106149

neuroscience4 · 4 ok
  • If secondary DAT activity is present (as suggested by the parent 2-AI pharmacology), mesolimbic dopamine pathway potentiation (ventral tegmental area projections to nucleus accumbens) would underlie the euphoria, motivation enhancement, and compulsive redosing urge described in community reportssupported

    2-AI is a substrate for NET and DAT. s00213-019-05207-1

  • Tirri et al. (2023) documented behavioral changes in mice consistent with entactogenic activity — including sensorimotor modulation and nociceptive alterations — while noting effects "appear atypical and less intense with respect to those induced by classic stimulants"supported

    Demonstrated entactogenic activity, mild hallucinogenic effect (PPI disruption). ijms24031882

  • Does the 2-AI metabolite significantly contribute to the overall effect? Tirri et al. (2023) identify 2-AI as the main active metabolite, but the relative contribution of parent NM-2-AI vs. metabolite 2-AI to the subjective experience is unquantified.supported

    Main active metabolite is 2-aminoindane (2-AI). ijms24031882

  • What is the alpha-2 adrenergic receptor activity of NM-2-AI? The parent 2-AI shows Ki = 41 nM at alpha-2C — whether NM-2-AI retains this affinity could significantly modulate its cardiovascular and CNS effects.supported

    High alpha2C receptor affinity (Ki=41 nM) s00213-019-05207-1

receptor-pharmacology4 · 2 ok
  • Claim in receptor-pharmacology — inconclusiveinconclusiveworking →

  • Halberstadt et al. (2019) confirmed 2-AI as a substrate at both NET and DAT and additionally characterized alpha-2 adrenergic receptor binding:supported

    2-AI is a substrate for NET and DAT. High alpha2C receptor affinity (Ki=41 nM), alpha2A (Ki=134 nM), alpha2B (Ki=211 nM). s00213-019-05207-1

  • Ring substitution at the 5,6-position (as in MDAI) shifts selectivity dramatically toward SERT, producing entactogenic rather than stimulant profilessupported

    Ring substitution increases SERT selectivity. s00213-019-05207-1

  • Claim in receptor-pharmacology — not_supportednot supportedworking →

chemistry1 · 1 ok
  • Two CAS registry numbers appear in the literature: 24445-44-1 (cited in Jurowski and Frydrych 2026) and 10408-85-2 (UNODC substance record)supported

    N-Methyl-2-aminoindane (NM-2-AI, CAS: 24445-44-1) j.tiv.2025.106149

clinical-evidence1 · 1 ok
  • Angerer et al. (2024) administered MDAI (180–228 mg oral) to six healthy volunteers in a crossover design comparing effects to 125 mg MDMA:supported

    MDAI (3.0 mg/kg, range 180-228 mg) in six healthy volunteers. MDAI produced effects comparable with 125 mg MDMA. dta.3622

effects-overview1 · 0 ok
  • Claim in effects-overview — not_supportednot supportedworking →

3Sources

20 consumed · sorted by year · feeds = sections resting on it

Sources
yearsourcetierstatusfeeds
2026First toxicity profile of 2-aminoindane and N-Methyl-2-aminoindane using in silico multi-approach.Jurowski K, Frydrych A · Toxicology in Vitrodoi:10.1016/j.tiv.2025.106149moderateconsumed3 sections
2024Acute psychotropic, autonomic, and endocrine effects of 5,6-methylenedioxy-2-aminoindane (MDAI) compared with 3,4-methylenedioxymethamphetamine (MDMA) in human volunteers: A self-administration study.Angerer V, Schmid Y, Franz F, Gnann H, Speer JM, Gnann A, Helmecke S, Buchwald A, Brandt SD, Passie T, Liechti ME, Auwärter V · Drug Testing and Analysisdoi:10.1002/dta.3622moderateconsumed2 sections
2023Behavioral and Pharmacokinetics Studies of N-Methyl-2-Aminoindane (NM2AI) in Mice: An Aminoindane Briefly Used in the Illicit Drug Market.Tirri M, Corli G, Arfe R, Marchetti B, Bilel S, Bernardi T, Boccuto F, Odoardi S, Mestria S, Strano-Rossi S, Marti M · International Journal of Molecular Sciencesdoi:10.3390/ijms24031882moderateconsumed6 sections
2021DEA Alert Regarding N-Methyl-2-Aminoindane (NM-2-AI)US Drug Enforcement Administrationurl:fe166c174cde9250weakconsumedcited only
2021Metabolism Study of N-Methyl 2-Aminoindane (NM2AI) and Determination of Metabolites in Biological Samples by LC-HRMS.Mestria S, Odoardi S, Federici S, Bilel S, Tirri M, Marti M, Strano Rossi S · Journal of Analytical Toxicologydoi:10.1093/jat/bkaa111moderateconsumed2 sections
2020N-Methyl-2-Aminoindane (NM-2-AI) Substance DetailsUnited Nations Office on Drugs and Crime (UNODC)url:c9b0d5c9d22058cdweakconsumedcited only
2020The metabolic fate of two new psychoactive substances - 2-aminoindane and N-methyl-2-aminoindane - studied in vitro and in vivo to support drug testing.Manier SK, Felske C, Eckstein N, Meyer MR · Drug Testing and Analysisdoi:10.1002/dta.2699moderateconsumed3 sections
20192-Aminoindan and its ring-substituted derivatives interact with plasma membrane monoamine transporters and alpha2-adrenergic receptorsHalberstadt A, Brandt S, Walther D, Baumann M · Psychopharmacologydoi:10.1007/s00213-019-05207-1moderateconsumed5 sections
2019Cytotoxicity of new psychoactive substances and other drugs of abuse studied in human HepG2 cells using an adopted high content screening assay.Richter LHJ, Beck A, Flockerzi V, Maurer HH, Meyer MR · Toxicology Lettersdoi:10.1016/j.toxlet.2018.11.007moderateconsumed2 sections
2019Death following consumption of MDAI and 5-EAPBDeville M, Dubois N, Cieckiewicz E, De Tullio P, Lemaire E, Charlier C · Forensic Science Internationaldoi:10.1016/j.forsciint.2019.03.023weakconsumed1 section
2017Synthetic Aminoindanes: A Summary of Existing Knowledge.Pinterova N, Horsley RR, Palenicek T · Frontiers in Psychiatrydoi:10.3389/fpsyt.2017.00236strongconsumed3 sections
2016A snapshot on NPS in Italy: Distribution of drugs in seized materials analysed in an Italian forensic laboratory in the period 2013-2015Odoardi S, Romolo FS, Strano-Rossi S · Forensic science internationaldoi:10.1016/j.forsciint.2016.01.037moderateconsumed1 section
2016Emerging toxicity of 5,6-methylenedioxy-2-aminoindane (MDAI): Pharmacokinetics, behaviour, thermoregulation and LD50 in rats.Palenicek T, Lhotkova E, Zidkova M, Balikova M, Kuchař M, Himl M, Miksatkova P, Cegan M, Vales K, Tylš F, Horsley RR · Progress in Neuro-Psychopharmacology & Biological Psychiatrydoi:10.1016/j.pnpbp.2016.04.004moderateconsumed2 sections
2016Locomotor, discriminative stimulus, and place conditioning effects of MDAI in rodents.Gatch MB, Dolan SB, Forster MJ · Behavioural Pharmacologydoi:10.1097/fbp.0000000000000237moderateconsumedcited only
2015Novel psychoactive substances (designer drugs): overview and pharmacology of modulators of monoamine signalingLiechti ME · Swiss Medical Weeklydoi:10.4414/smw.2015.14043moderateconsumed2 sections
2014Pharmacological profiles of aminoindanes, piperazines, and pipradrol derivatives.Simmler LD, Rickli A, Schramm Y, Hoener MC, Liechti ME · Biochemical Pharmacologydoi:10.1016/j.bcp.2014.01.024moderateconsumed4 sections
2003Safety, pharmacokinetics, and pharmacodynamics of CHF 3381, a novel N-methyl-D-aspartate antagonist, after single oral doses in healthy subjects.Tarral A, Dostert P, Guillevic Y, et al. · Journal of Clinical Pharmacologypmid:12953347moderateconsumed2 sections
1991Serotonin neurotoxicity in rats after combined treatment with a dopaminergic agent followed by a nonneurotoxic MDMA analogue.Johnson MP, Huang XM, Nichols DE · Pharmacology, Biochemistry, and Behaviorpmid:1726189moderateconsumed1 section
1990(+)-N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine as a discriminative stimulus in studies of MDMA-like behavioral activity.Oberlender R, Nichols DE · Journal of Pharmacology and Experimental Therapeuticspmid:1979813moderateconsumed1 section
1980In vitro actions of NN-dimethyl-2-aminoindane and related compounds.Little HJ, Rees JM · Journal of Pharmacy and Pharmacologypmid:6110722moderateconsumed2 sections
—Aminoindanes (UNODC Substance Group Details)url:a65631070cc434c9—unknowncited only
—Searched ClinicalTrials.gov for "aminoindane NM-2-AI 2-aminoindane" — no resultsabsenceno results—

4Docket

one filing per activity — decisions, correspondence, reports

  1. 0012026-05-11revisionRevision 1

    Initial LLM generation (v5 pipeline, wiki, prose phase)

    psx:substance/nm-2-ai/version/1
  2. 0022026-06-04proposal29 value proposals approved together

    one review action inferred from a shared reviewer and instant — the graph records one activity per proposal

    29 items in this filing

    • contraindication · cardiovascular
    • contraindication · cardiovascular
    • contraindication · neurological
    • contraindication · hepatic
    • contraindication · psychiatric
    • contraindication · psychiatric
    • contraindication · pregnancy_breastfeeding
    • dose_tier · threshold
    • dose_tier · light
    • dose_tier · common
    • dose_tier · strong
    • dose_tier · heavy
    • timeline · oral · onset
    • timeline · oral · come_up
    • timeline · oral · peak
    • timeline · oral · resolution
    • timeline · oral · afterglow
    • toxicity
    • dependence · full
    • withdrawal
    • tolerance
    • dosage · oral
    • duration · oral · onset
    • duration · oral · come_up
    • duration · oral · peak
    • duration · oral · offset
    • duration · oral · total
    • duration · oral · aftereffects
    psx:substance/nm-2-ai/proposal/contraindication/43c0e008-8407-47af-adec-f68a7c25275e
  3. 0032026-06-04publicationPublication — backfill
  4. 0042026-10-02rulingRuling — psx:substance/nm-2-ai/proposal/article_section_proposals/31f2476e-5a3c-4a47-9794-d1c63df1f55ffounder
  5. 0052026-10-02rulingRuling — psx:substance/nm-2-ai/proposal/article_section_proposals/b0ff84c8-b65b-46d0-86e3-2372adf6356ffounder
  6. 0062026-10-02revisionr1.a1

    no edit summary recorded

    psx:substance/nm-2-ai/version/2
  7. 0072026-10-02publicationPublication — publishagent-psx

5Issued documents

what the notice, info card and emergency page said, by hash

Issued documents
documentcontent hashissuedfrom versionsuperseded
info_card6aa1b5414907aaf30be968d9…2026-10-02 13:09Revision 2current
emergency47cf1475db8db7f236c6a01a…2026-09-04 04:31Revision 1current
info_cardd10920af086643b23ccea258…2026-09-04 04:31Revision 1superseded2026-10-02
notice84f4bc5a1bdf4b7c61664b60…2026-09-04 04:31Revision 1current