generation run 2026-05-03
66 min completedmodel pipeline-v5plan not recordedrun/cae57732…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
none raised on this run
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
- 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 | WebSearch | MDAI David Nichols aminoindane synthesis 1990s original paper | 10 | 1 | Confirmed PubMed finding, added context on synthesis history |
| 2 | PubMed | MDAI aminoindane serotonin transporter binding | 2 | 0 | Duplicates of already-found papers |
| 3 | OpenAlex | MDAI 5,6-methylenedioxy-2-aminoindane pharmacology | 55 | 2 | Selected major review papers covering MDAI; other high-citation papers were broader NPS reviews not MDAI-specific |
| 4 | ClinicalTrials.gov · absence | MDAI aminoindane | 0 | 0 | No registered trials exist |
| 5 | PubChem | MDAI | 1 | 1 | Primary chemical identity data verified |
| 6 | PubMed | Nichols Brewster Johnson nonneurotoxic tetralin indan MDA 1990 | 1 | 1 | Foundational synthesis and discovery paper for MDAI |
| 7 | PubMed | MDAI 5,6-methylenedioxy-2-aminoindane pharmacology | 15 | 14 | All directly relevant to MDAI pharmacology, toxicology, or clinical reports |
| 8 | PMC (Pinterova 2017 full text) | MDAI pharmacology Ki EC50 legal status clinical data | 1 | 3 | Primary comprehensive review; confirmed multiple data points |
| 9 | Erowid MDAI Law | MDAI legal status | 1 | 4 | Primary legal status source |
| 10 | DOI Crossref verification | Multiple DOI verifications | 5 | 1 | Verification of source authenticity |
| 11 | WebSearch | MDAI SERT NET DAT EC50 Ki pharmacology values | 10 | 3 | Critical pharmacological data |
| 12 | Release UK MDAI law page | MDAI UK legal status | 1 | 1 | UK-specific legal status |
| 13 | PubChem REST API | CID 125558 chemical properties | 1 | 2 | Chemical identity verification |
| 14 | WebSearch | MDAI CAS number 132741-81-2 melting point | 10 | 2 | Physical property data |
| 15 | ClinicalTrials.gov · absence | MDAI aminoindane | 0 | 0 | Confirms absence of formal clinical trial program |
90 claims by section — every cited sentence, checked against its source
safety26 · 20 ok
The most comprehensive acute toxicity data derive from a study in Wistar rats:supported
SC LD50 = 28.33 mg/kg, IV LD50 = 35 mg/kg in Wistar rats. Brain/serum ratio ~4. Peak serum/brain concentrations at 30min post-SC dose; near zero by 6h. Lung accumulation. DIC and cerebral edema as mechanisms of death. Hyperthermia in group-housed rats. j.pnpbp.2016.04.004
Claim in safety — inconclusiveinconclusiveworking →
The mechanism of death in rats was disseminated intravascular coagulopathy (DIC) with cerebral edemasupported
DIC and cerebral edema as mechanisms of death. j.pnpbp.2016.04.004
Claim in safety — not_supportednot supportedworking →
In vitro screening in human HepG2 cells (hepatocellular carcinoma line) classified MDAI among the most cytotoxic compounds tested, with toxicity exceeding MDMA, MDPV, methylone, cathinone, 4-MEC, and mephedronesupported
Study showed strong cytotoxic potential for MDAI (along with 5F-PB-22), moderate effects for MDMA, MDPV, methylone, cathinone, 4-MEC, and mephedrone, and no toxic effects for methamphetamine in HepG2 cells. j.toxlet.2018.11.007
Claim in safety — inconclusiveinconclusiveworking →
However, no body temperature increase was observed in human subjects at 3 mg/kg oral under controlled conditionssupported
MDAI increased blood pressure similar to 125 mg MDMA but did not increase heart rate or body temperature. dta.3622
A case of acquired methaemoglobinaemia was reported in a psychiatric inpatient who consumed "Pink Panthers," a product containing MDAI and 2-aminoindanesupported
Case of acquired methaemoglobinaemia due to use of 'Pink Panthers' legal high containing 5,6-Methylenedioxy-2-aminoindane and 2-Aminoindane. thoraxjnl-2014-205769
UK, 2011–2012: Three deaths involving MDAI, with serotonin syndrome implicated as a probable contributing mechanism. Combination drug use was identified in all cases.supported
Overview of MDAI including first three UK deaths in 2011 and 2012. Serotonin syndrome implicated. hup.2298
Belgium, 2019: A 28-year-old male found dead with postmortem blood concentrations of MDAI 2.09 mg/L and 5-EAPB 6.45 mg/L, with additional 5-MAPB (0.089 mg/L) and 5-APB (0.546 mg/L) detected. Death attributed to combined NPS consumption.supported
Case report of a 28-year-old man found dead with MDAI (68% purity powder) and 5-EAPB. Blood concentrations: MDAI 2.09 mg/L, 5-EAPB 6.45 mg/L. 5-MAPB and 5-APB also detected. Cause of death attributed to polydrug NPS consumption. j.forsciint.2019.03.023
Zurich, 2017: Fatal case involving MDAI and 2-MAPB. An antemortem blood sample was available (collected 6 hours before death). DIC and cerebral edema were consistent with rat toxicology findings.partially supported
Fatal case involving MDAI and 2-MAPB; antemortem blood sample collected 6h before death available. First study on postmortem redistribution of MDAI and 2-MAPB. j.forsciint.2017.08.007
Serotonin syndrome — characterized by agitation, hyperthermia, clonus, hyperreflexia, diaphoresis, and tremor — was identified as a probable contributing mechanism in the first UK deaths involving MDAIsupported
Overview of MDAI including first three UK deaths in 2011 and 2012. Serotonin syndrome implicated. hup.2298
Claim in safety — inconclusiveinconclusiveworking →
Conditioned place preference was demonstrated in mice across a dose range of 0.3–10 mg/kg intraperitoneal, confirming positive reinforcing propertiessupported
Conditioned place preference from 0.3 to 10 mg/kg ip. fbp.0000000000000237
However, the weak DAT activity (DA release EC₅₀ = 24 μM) predicts substantially lower mesolimbic reinforcement and incentive salience than dopamine-dominant stimulantssupported
MDAI has higher potency at hSERT than hDAT, predicting empathogen psychoactivity. jpet.116.236349
Eshleman and colleagues noted that compounds with high SERT-to-DAT potency ratios (as with MDAI) possess "potential empathogen psychoactivity" but lower addiction liability than DAT-selective compoundssupported
MDAI has higher potency at hSERT than hDAT, predicting empathogen psychoactivity. jpet.116.236349
The Belgium fatality involved simultaneous exposure to MDAI, 5-EAPB, 5-MAPB, and 5-APB — all serotonergic benzofuran derivativessupported
Blood concentrations: MDAI 2.09 mg/L, 5-EAPB 6.45 mg/L. 5-MAPB and 5-APB also detected. j.forsciint.2019.03.023
The Zurich case involved MDAI with 2-MAPBsupported
Fatal case involving MDAI and 2-MAPB. j.forsciint.2017.08.007
Co-administration with 2-aminoindane produced methaemoglobinaemia in at least one documented casesupported
Case of acquired methaemoglobinaemia due to use of 'Pink Panthers' legal high containing 5,6-Methylenedioxy-2-aminoindane and 2-Aminoindane. thoraxjnl-2014-205769
Claim in safety — inconclusiveinconclusiveworking →
All documented MDAI fatalities involved serotonergic polydrug exposure.supported
Cause of death attributed to polydrug NPS consumption. j.forsciint.2019.03.023
All documented MDAI fatalities involved serotonergic polydrug exposure.supported
Fatal case involving MDAI and 2-MAPB. j.forsciint.2017.08.007
Pre-existing cardiovascular conditions constitute a relative contraindication: MDAI elevates blood pressure at doses producing subjective effects, and norepinephrine release (EC₅₀ = 0.57 μM) produces sympathomimetic cardiovascular stress.supported
MDAI was well tolerated and produced subjective effects comparable with those of 125 mg MDMA. MDAI increased blood pressure similar to 125 mg MDMA but did not increase heart rate or body temperature. dta.3622
Pre-existing cardiovascular conditions constitute a relative contraindication: MDAI elevates blood pressure at doses producing subjective effects, and norepinephrine release (EC₅₀ = 0.57 μM) produces sympathomimetic cardiovascular stress.supported
MDAI and 4-MEC were substrates primarily at hSERT and hNET. jpet.116.236349
Hepatic impairment is a relative contraindication based on the strong in vitro hepatotoxicity signal in HepG2 cells, though no human hepatotoxicity cases have been reported.supported
Study showed strong cytotoxic potential for MDAI (along with 5F-PB-22), moderate effects for MDMA, MDPV, methylone, cathinone, 4-MEC, and mephedrone. j.toxlet.2018.11.007
Claim in safety — inconclusiveinconclusiveworking →
pharmacology13 · 6 ok
Rather than blocking transporter-mediated reuptake (as with SSRIs), MDAI enters presynaptic neurons via monoamine transporters and triggers carrier-mediated efflux of stored neurotransmitters — a mechanism shared with MDMA, MDA, and the amphetamines.supported
MDAI preferentially inhibited SERT and NET and released 5-HT. Weak DAT activity. Characterized using HEK293 cells expressing human monoamine transporters. j.bcp.2014.01.024
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Eshleman and colleagues explicitly classified MDAI as a substrate "primarily at hSERT and hNET".supported
MDAI and 4-MEC were substrates primarily at hSERT and hNET. jpet.116.236349
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
The original characterization by Nichols and colleagues established that a single 40 mg/kg subcutaneous dose of MDAI did not depress rat cortical or hippocampal serotonin, 5-HIAA, or [³H]paroxetine binding sites — unlike MDMA, which significantly depleted all three markers at the same dosesupported
Did not depress cortical/hippocampal 5-HT, 5-HIAA or [3H]paroxetine binding sites. Original synthesis and non-neurotoxicity characterization paper. pmid:1967651
Human pharmacokinetic data for MDAI derive from a single non-blinded study (N = 6) in which participants self-administered approximately 3.0 mg/kg oral (range 180–228 mg)supported
MDAI (3.0 mg/kg, range 180-228 mg) were investigated in six healthy volunteers in a non-blinded fashion without placebo. dta.3622
Claim in pharmacology — inconclusiveinconclusiveworking →
Rat pharmacokinetic data (10 mg/kg subcutaneous) demonstrate peak serum and brain concentrations at 30 minutes post-dose, with near-zero concentrations by 6 hourssupported
Peak serum/brain concentrations at 30min post-SC dose; near zero by 6h. j.pnpbp.2016.04.004
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
Postmortem analysis of a fatal case demonstrated that MDAI does not undergo significant redistribution between peripheral and central blood compartments — unlike many lipophilic drugs — potentially simplifying forensic toxicological interpretation.supported
MDAI did not undergo relevant postmortem redistribution in peripheral or heart blood. j.forsciint.2017.08.007
summary11 · 4 ok
Claim in summary — inconclusiveinconclusiveworking →
MDAI was synthesized in 1990 by David Nichols and colleagues at Purdue University as part of a program to design MDMA-like compounds lacking serotonergic neurotoxicitysupported
Original synthesis and non-neurotoxicity characterization paper. pmid:1967651
The compound remained a laboratory tool until approximately 2007, when it appeared on European recreational markets, with uptake accelerating after the UK scheduling of mephedrone in 2010supported
Widely advertised as legal alternative after mephedrone was banned UK April 2010. hup.1255
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
At 3 mg/kg oral, effects were rated comparable to 125 mg MDMA on standardized scales, with blood pressure elevation but without the heart rate or body temperature increases characteristic of MDMAsupported
MDAI was well tolerated and produced subjective effects comparable with those of 125 mg MDMA. MDAI increased blood pressure similar to 125 mg MDMA but did not increase heart rate or body temperature. dta.3622
Claim in summary — inconclusiveinconclusiveworking →
All documented human fatalities have involved polydrug combinations with other serotonergic substances; no deaths from MDAI alone are confirmedsupported
Cause of death attributed to polydrug NPS consumption. j.forsciint.2019.03.023
Claim in summary — inconclusiveinconclusiveworking →
history10 · 9 ok
Critically, a single dose of 40 mg/kg subcutaneous MDAI did not depress rat cortical or hippocampal serotonin, 5-HIAA, or [³H]paroxetine binding sites — unlike MDMA at the same dose, which produced significant depletion of all three markers.supported
Did not depress cortical/hippocampal 5-HT, 5-HIAA or [3H]paroxetine binding sites. pmid:1967651
The results appeared in the Journal of Medicinal Chemistry in February 1990, where MDAI was designated compound 3a and described as 5,6-methylenedioxy-2-aminoindan.supported
MDAI (compound 3a, 5,6-methylenedioxy-2-aminoindan). pmid:1967651
A follow-up publication in 1991 by Nichols, Johnson, and Oberlender extended this work to 5-iodo-2-aminoindan (5-IAI), which similarly demonstrated non-neurotoxic properties, confirming the aminoindane scaffold as a general strategy for producing entactogens without serotonergic damagesupported
5-IAI (rigid aminoindane analogue of p-iodoamphetamine) evaluated for serotonin neurotoxicity. Confirms non-neurotoxic design of aminoindane scaffold. pmid:1826785
MDAI first appeared in European recreational drug markets around 2007supported
Recreational use started in Europe around 2007, increased after 2009 in UK. hup.2298
The regulatory vacuum left by mephedrone's prohibition created immediate commercial demand for legal alternatives, and MDAI was widely advertised as a substitute, sold through online vendors and head shops under street names including "sparkle" and "mindy".supported
Widely advertised as legal alternative after mephedrone was banned UK April 2010. hup.1255
The regulatory vacuum left by mephedrone's prohibition created immediate commercial demand for legal alternatives, and MDAI was widely advertised as a substitute, sold through online vendors and head shops under street names including "sparkle" and "mindy".supported
Recreational use started in Europe around 2007, increased after 2009 in UK. hup.2298
The compound was also marketed in combination products. "Pink Panthers," a widely distributed preparation, contained both MDAI and 2-aminoindanesupported
Case of acquired methaemoglobinaemia due to use of 'Pink Panthers' legal high containing 5,6-Methylenedioxy-2-aminoindane and 2-Aminoindane. thoraxjnl-2014-205769
Gallagher and colleagues characterized MDAI's trajectory as a transition "from laboratory curiosity to 'legal high,'" noting that the compound's non-neurotoxic reputation — derived from the 1990 Nichols paper — was a significant marketing asset in online drug communities.supported
Overview of MDAI: developed in 1990s, not widely abused until 2010. Widely advertised as legal alternative after mephedrone was banned UK April 2010. hup.1255
The first UK deaths involving MDAI were reported in 2011–2012, prompting increased regulatory scrutinysupported
Overview of MDAI including first three UK deaths in 2011 and 2012. hup.2298
Claim in history — inconclusiveinconclusiveworking →
neuroscience9 · 5 ok
What explains the temperature discrepancy between species? Rats show hyperthermia at 10–20 mg/kg subcutaneous, while human subjects showed no temperature elevation at 3 mg/kg oral. Whether this reflects species-specific thermoregulation, route and dose differences, or environmental conditions (clinical setting versus grouped housing) remains unknown.supported
Hyperthermia in group-housed rats. j.pnpbp.2016.04.004
What explains the temperature discrepancy between species? Rats show hyperthermia at 10–20 mg/kg subcutaneous, while human subjects showed no temperature elevation at 3 mg/kg oral. Whether this reflects species-specific thermoregulation, route and dose differences, or environmental conditions (clinical setting versus grouped housing) remains unknown.supported
MDAI increased blood pressure similar to 125 mg MDMA but did not increase heart rate or body temperature. dta.3622
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
The cortisol elevation observed in human subjects is consistent with serotonergically-mediated hypothalamic-pituitary-adrenal (HPA) axis activation.supported
MDAI increased cortisol and prolactin levels. dta.3622
Claim in neuroscience — inconclusiveinconclusiveworking →
Prolactin elevation in MDAI-treated human subjects confirms serotonergic neuroendocrine activation, and oxytocin release is predicted by pharmacological class, though it was not directly measured.supported
MDAI increased cortisol and prolactin levels. dta.3622
The behavioral pattern observed (initial locomotor depression followed by rebound stimulation) suggests complex temporal dynamics in monoaminergic circuit activation.supported
Depression then rebound stimulation of locomotion. fbp.0000000000000237
Claim in neuroscience — inconclusiveinconclusiveworking →
pharmacokinetic-detail7 · 6 ok
The sole human pharmacokinetic dataset derives from a non-blinded self-administration study (N = 6, no placebo control) in which healthy volunteers took approximately 3.0 mg/kg MDAI orally (absolute dose range: 180–228 mg for participants weighing 60–76 kg).supported
MDAI (3.0 mg/kg, range 180-228 mg) were investigated in six healthy volunteers in a non-blinded fashion without placebo. dta.3622
Rat pharmacokinetic data (10 mg/kg subcutaneous, Wistar rats) provide additional detail:supported
SC LD50 = 28.33 mg/kg, IV LD50 = 35 mg/kg in Wistar rats. Brain/serum ratio ~4. Peak serum/brain concentrations at 30min post-SC dose; near zero by 6h. j.pnpbp.2016.04.004
A fatal case study demonstrated that MDAI does not undergo significant postmortem redistribution between peripheral and central blood compartmentssupported
MDAI did not undergo relevant postmortem redistribution in peripheral or heart blood. j.forsciint.2017.08.007
The extended detection windows (serum ≥ 4 days, urine ≥ 6 days) suggest a substantially longer elimination phase than MDMA, though the absence of a calculated half-life prevents direct pharmacokinetic comparisonsupported
MDAI could be detected in serum about 20 min post ingestion and remained detectable at least for 4 days. In urine, MDAI was detectable over a period of at least 6 days. dta.3622
The brain-to-serum ratio of approximately 4 confirms rapid and efficient CNS penetration, consistent with the moderate lipophilicity (XLogP 1.2)supported
Brain/serum ratio ~4. j.pnpbp.2016.04.004
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
A significant concentration decrease was observed between the antemortem sample (collected 6 hours before death) and the first postmortem sample, attributed to ongoing metabolism and excretion during the intervening period rather than redistribution artifact.supported
Fatal case involving MDAI and 2-MAPB; antemortem blood sample collected 6h before death available. MDAI did not undergo relevant postmortem redistribution in peripheral or heart blood. j.forsciint.2017.08.007
comparative-pharmacology5 · 3 ok
However, MDAI fully substituted for DOM (a 5-HT₂A agonist) in drug discrimination assays in rats at 5 mg/kg, suggesting that serotonin release from MDAI may activate 5-HT₂A receptors indirectly at sufficient doses.supported
MDAI fully substituted for MDMA, DOM, and cocaine discriminative stimuli. fbp.0000000000000237
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
The aminoindane class includes several compounds with distinct pharmacological profiles. 5-IAI (5-iodo-2-aminoindan), also developed by Nichols, shares the non-neurotoxic property and was characterized in a 1991 follow-up study. 2-Aminoindane (2-AI), the unsubstituted parent compound, lacks the methylenedioxy bridge and has been marketed in combination with MDAIsupported
5-IAI (rigid aminoindane analogue of p-iodoamphetamine) evaluated for serotonin neurotoxicity. Confirms non-neurotoxic design of aminoindane scaffold. pmid:1826785
The aminoindane class includes several compounds with distinct pharmacological profiles. 5-IAI (5-iodo-2-aminoindan), also developed by Nichols, shares the non-neurotoxic property and was characterized in a 1991 follow-up study. 2-Aminoindane (2-AI), the unsubstituted parent compound, lacks the methylenedioxy bridge and has been marketed in combination with MDAIsupported
Case of acquired methaemoglobinaemia due to use of 'Pink Panthers' legal high containing 5,6-Methylenedioxy-2-aminoindane and 2-Aminoindane. thoraxjnl-2014-205769
clinical-evidence4 · 2 ok
Angerer and colleagues conducted a self-administration study in 6 healthy volunteers who took approximately 3.0 mg/kg MDAI orally (absolute dose range: 180–228 mg)supported
MDAI (3.0 mg/kg, range 180-228 mg) were investigated in six healthy volunteers in a non-blinded fashion without placebo. dta.3622
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Claim in clinical-evidence — inconclusiveinconclusiveworking →
The finding that MDAI produces MDMA-comparable subjective effects without heart rate or temperature elevation raises the possibility of a more favorable cardiovascular safety profile for entactogen-assisted therapysupported
MDAI was well tolerated and produced subjective effects comparable with those of 125 mg MDMA. MDAI increased blood pressure similar to 125 mg MDMA but did not increase heart rate or body temperature. dta.3622
receptor-pharmacology3 · 0 ok
chemistry2 · 1 ok
MDAI specifically incorporates a 5,6-methylenedioxy substitution on the aromatic ring, making it a direct structural analogue of MDA in which the side chain is cyclized into the indane system.supported
Drug discrimination study of cyclic MDA analogues. MDAI (compound 3a, 5,6-methylenedioxy-2-aminoindan). pmid:1967651
Claim in chemistry — inconclusiveinconclusiveworking →