Chemical compound
Pharmaceutical compound
MEAI , also known as5-methoxy-2-aminoindane (5-MeO-AI ), is amonoamine releasing agent of the2-aminoindane group.[ 1] selective serotonin releasing agent (SSRA).[ 1] alcoholism ,cocaine use disorder ,metabolic syndrome , andobesity under the developmental code nameCMND-100 .[ 2]
When usedrecreationally , MEAI is reported to produce mildpsychoactive effects andeuphoria .[ 1]
MEAI is amonoamine releasing agent (MRA).[ 1] selective serotonin releasing agent (SSRA), with 6-fold preference for induction ofserotonin release overnorepinephrine release and 20-fold preference for induction of serotonin release overdopamine release.[ 1] monoamine neurotransmitter release, MEAI has moderateaffinity for theα2 -adrenergic receptor .[ 1] MDMA -likeentactogenic andsympathomimetic effects but may be expected to have reducedmisuse liability in comparison.[ 1]
MEAI, also known as 5-methoxy-2-aminoindane, is a2-aminoindane derivative .[ 12] analogue of theamphetamine 3-methoxyamphetamine .[ 12]
MEAI appears to have been firstsynthesized in 1956.[ 1] markush structure schema appearing in a patent from 1998.[ 13] David Nutt and Ezekiel Golan et al.[ 14] pharmacokinetics ,pharmacodynamics and metabolism of MEAI by Shimshoni, David Nutt, Ezekiel Golan et al.[ 15] [ 16] [ 17] [ 18]
MEAI was an early candidate ofalcohol replacement drugs that came to market during a late 2010s movement to replace alcohol with less-toxic alternatives spearheaded by Britishpsychopharmacologist David Nutt [ 19] [ 20] [ 21] [ 22]
In an act ofgonzo journalism , Michael Slezak writing forNew Scientist , tried and reported on his experience with MEAI[ 23] [ 24] [ 23] DrugScience . The goal was to develop MEAI further based on Golan's patents as a "binge behaviour regulator"[ 25] [ 26]
In 2018, a company named Diet Alcohol Corporation of the Americas (DACOA) began openly marketing an MEAI-based drink called "Pace" for sale in the USA and Canada. Pace was described as a 50ml bottle containing 160 mg of MEAI in mineral water. Distribution halted afterHealth Canada released a warning indicating the substance was considered illegal to market for consumption in Canada due to structural similarity to amphetamine.[ 27] [ 28] CBC News , Dr Zee (Ezekiel Golan) was interviewed and publicly came out as the "lead scientist" of Pace claiming "tens of thousands" of bottles were already sold in Canada.[ 29] [ 29] Health Canada provided a statement to CBC News stating "Pace is an illegal and unauthorized product in Canada."
Clinical development [ edit ] On May 26, 2022, MEAI was prepared forFDA registration byClearmind Medicine Inc. ;[ 30] [ 31] [ 32] [ 33] [ 34] [ 35] [ 36] [ 37] [ 38] [ 39]
MEAI, under the developmental code name CMND-100, is under development by Clearmind Medicine for the treatment ofalcoholism ,cocaine use disorder ,metabolic syndrome , andobesity .[ 2] preclinical stage of development for these indications.[ 2]
^a b c d e f g h i j k l m Halberstadt AL, Brandt SD, Walther D, Baumann MH (March 2019)."2-Aminoindan and its ring-substituted derivatives interact with plasma membrane monoamine transporters and α2-adrenergic receptors" .Psychopharmacology (Berl) .236 (3):989– 999.doi :10.1007/s00213-019-05207-1 .PMC 6848746 PMID 30904940 . ^a b c "Revolutionary Psychedelics for Treating Addiction & Mental Health" .Clearmind . 16 December 2024. Retrieved16 March 2025 .^a b Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS (January 2001). "Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin".Synapse .39 (1):32– 41.doi :10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3 .PMID 11071707 .S2CID 15573624 . ^ Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, Rothman RB, Goldberg SR, Lupica CR, Sitte HH, Brandt SD, Tella SR, Cozzi NV, Schindler CW (March 2013)."Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products" .Neuropsychopharmacology .38 (4):552– 562.doi :10.1038/npp.2012.204 .PMC 3572453 PMID 23072836 . ^a b c Blough B (July 2008)."Dopamine-releasing agents" (PDF) . In Trudell ML, Izenwasser S (eds.).Dopamine Transporters: Chemistry, Biology and Pharmacology 305– 320.ISBN 978-0-470-11790-3 OCLC 181862653 .OL 18589888W . ^ Glennon RA, Dukat M (2017). "Structure-Activity Relationships of Synthetic Cathinones".Neuropharmacology of New Psychoactive Substances (NPS) . Current Topics in Behavioral Neurosciences. Vol. 32. pp. 19– 47.doi :10.1007/7854_2016_41 .ISBN 978-3-319-52442-9 PMC 5818155 PMID 27830576 . ^ Partilla JS, Dersch CM, Baumann MH, Carroll FI, Rothman RB (1999). "Profiling CNS Stimulants with a High-Throughput Assay for Biogenic Amine Transporter Substractes".Problems of Drug Dependence 1999: Proceedings of the 61st Annual Scientific Meeting, The College on Problems of Drug Dependence, Inc (PDF) . NIDA Res Monogr. Vol. 180. pp. 1–476 (252).PMID 11680410 . Archived fromthe original (PDF) on August 5, 2023.RESULTS. Methamphetamine and amphetamine potently released NE (IC50s = 14.3 and 7.0 nM) and DA (IC50s = 40.4 nM and 24.8 nM), and were much less potent releasers of 5-HT (IC50s = 740 nM and 1765 nM). [...] ^a b Setola V, Hufeisen SJ, Grande-Allen KJ, Vesely I, Glennon RA, Blough B, Rothman RB, Roth BL (June 2003). "3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro".Molecular Pharmacology .63 (6):1223– 1229.doi :10.1124/mol.63.6.1223 .PMID 12761331 .S2CID 839426 . ^a b Brandt SD, Walters HM, Partilla JS, Blough BE, Kavanagh PV, Baumann MH (December 2020)."The psychoactive aminoalkylbenzofuran derivatives, 5-APB and 6-APB, mimic the effects of 3,4-methylenedioxyamphetamine (MDA) on monoamine transmission in male rats" .Psychopharmacology (Berl) .237 (12):3703– 3714.doi :10.1007/s00213-020-05648-z .PMC 7686291 PMID 32875347 . ^ Baumann MH, Ayestas MA, Partilla JS, Sink JR, Shulgin AT, Daley PF, Brandt SD, Rothman RB, Ruoho AE, Cozzi NV (April 2012)."The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue" .Neuropsychopharmacology .37 (5):1192– 1203.doi :10.1038/npp.2011.304 .PMC 3306880 PMID 22169943 . ^ Marusich JA, Antonazzo KR, Blough BE, Brandt SD, Kavanagh PV, Partilla JS, Baumann MH (February 2016)."The new psychoactive substances 5-(2-aminopropyl)indole (5-IT) and 6-(2-aminopropyl)indole (6-IT) interact with monoamine transporters in brain tissue" .Neuropharmacology .101 :68– 75.doi :10.1016/j.neuropharm.2015.09.004 .PMC 4681602 PMID 26362361 . ^a b Nichols DE, Marona-Lewicka D, Huang X, Johnson MP (1993)."Novel serotonergic agents" .Drug des Discov .9 (3– 4):299– 312.PMID 8400010 . ^ US 5708018 , Haadsma-Svensson SR, Andersson BR, Sonesson CA, Lin CH, Waters RN, Svensson KA, Carlsson PA, Hansson LO, Stjernlof NP, "2-aminoindans as selective dopamine D3 ligands", published 1998-01-13, assigned toPharmacia & Upjohn Co. ^ Shimshoni JA, Winkler I, Edery N, Golan E, van Wettum R, Nutt D (March 2017). "Toxicological evaluation of 5-methoxy-2-aminoindane (MEAI): Binge mitigating agent in development".Toxicology and Applied Pharmacology .319 :59– 68.Bibcode :2017ToxAP.319...59S .doi :10.1016/j.taap.2017.01.018 .PMID 28167221 .S2CID 205304106 . ^ Shimshoni JA, Sobol E, Golan E, Ben Ari Y, Gal O (March 2018). "Pharmacokinetic and pharmacodynamic evaluation of 5-methoxy-2-aminoindane (MEAI): A new binge-mitigating agent".Toxicology and Applied Pharmacology .343 :29– 39.Bibcode :2018ToxAP.343...29S .doi :10.1016/j.taap.2018.02.009 .PMID 29458138 .S2CID 3879333 . ^ Halberstadt AL, Brandt SD, Walther D, Baumann MH (March 2019)."2-Aminoindan and its ring-substituted derivatives interact with plasma membrane monoamine transporters and α2 -adrenergic receptors" .Psychopharmacology .236 (3):989– 999.doi :10.1007/s00213-019-05207-1 .PMC 6848746 PMID 30904940 . ^ Sainsbury PD, Kicman AT, Archer RP, King LA, Braithwaite RA (2011). "Aminoindanes--the next wave of 'legal highs'?".Drug Testing and Analysis .3 (7– 8):479– 482.doi :10.1002/dta.318 .PMID 21748859 . ^ Cannon JG, Perez JA, Pease JP, Long JP, Flynn JR, Rusterholz DB, Dryer SE (July 1980). "Comparison of biological effects of N-alkylated congeners of beta-phenethylamine derived from 2-aminotetralin, 2-aminoindan, and 6-aminobenzocycloheptene".Journal of Medicinal Chemistry .23 (7):745– 749.doi :10.1021/jm00181a009 .PMID 7190613 . ^ Nutt D (23 October 2013)."Decision making about illegal drugs: time for science to take the lead" .Nobel Forum, Karolinska Institutet – viaYouTube . ^ Nutt DJ, King LA, Phillips LD (November 2010). "Drug harms in the UK: a multicriteria decision analysis".Lancet .376 (9752). London, England:1558– 65.doi :10.1016/S0140-6736(10)61462-6 .PMID 21036393 .S2CID 5667719 . ^ Forster K (24 September 2016)."Hangover free alcohol is finally here" .The Independent . Retrieved25 March 2022 . ^ Wermter B (29 April 2019)."Rauschmittel und gesellschaftliche Probleme" [Drug related societal issues].Benedict Wermter (in German). ^a b Slezak M (30 December 2014)."High and dry? Party drug could target excess drinking" .New Scientist . Retrieved2022-10-16 . ^ Slezak M (9 August 2014)."An Interview with Dr Z" (PDF) .New Scientist . pp. 1– 3. Retrieved16 October 2022 . ^ US 10406123B2 , Golan E, "Binge behavior regulators", issued 2019-09-10 ^ US 20170360067 , Golan E, "Alcoholic beverage substitutes", issued 2017-12-21 ^ "Advisory - Health Canada warns consumers that Pace, promoted as an alcohol substitute, is unauthorized and may pose serious health risks" .Health Canada . 21 December 2018 – via CISION.^ Brunet J (24 April 2019)."FACT CHECK: Is Pace, an "Alcohol Alternative," Legal in Canada?" .The Walrus . Toronto, Ontario. ^a b Wright J (8 December 2018)."Is this drink really a new 'alcohol alternative'?" .Information Morning Saint John . pp. All. Retrieved15 October 2022 . ^ "Clearmind Medicine" .www.clearmindmedicine.com .^ "Clearmind Medicine Inc" .CSE:CMND .^ וינרב, גלי (16 February 2022)."החברה שמנסה להפוך סם פסיכדלי למוצר נגד התמכרות" [The company trying to turn a psychedelic drug into an anti-addiction product].Globes (in Hebrew). ^ US 10137096 , Golan E, "Binge behavior regulators", published 2018-11-27 ^ EP 3230256 , Golan E, "Alcoholic beverage substitutes", published 2019-11-13 ^ EP 3230255 , Golan E, "Binge behavior regulators", published 2017-10-18 ^ "The Science and IP Behind our Treatments" .Clearmind .^ "Clearmind Medicine" .www.clearmindmedicine.com .^ "Clearmind Medicine" .www.clearmindmedicine.com . Retrieved14 August 2022 .^ "Clearmind Medicine" .www.clearmindmedicine.com . Retrieved2022-10-16 .
DRAs Tooltip Dopamine releasing agents
NRAs Tooltip Norepinephrine releasing agents
SRAs Tooltip Serotonin releasing agents
Others
Phenethylamines Amphetamines Phentermines Cathinones Phenylisobutylamines (and further-extended) Catecholamines (and close relatives) Cyclized
Phenylalkylpyrrolidines 2-Benzylpiperidines (phenidates ) Phenylmorpholines (phenmetrazines) Phenyloxazolamines (aminorexes) Isoquinolines andtetrahydroisoquinolines 2-Aminoindanes 2-Aminotetralins Others / unsorted 1-Aminomethylindanes (e.g.,2CB-Ind ,AMMI ,bromojimscaline ,jimscaline )2-ADN 2-Benzhydrylpyrrolidine 2C-B-5-hemiFLY-α6 (BNAP) 2C-B-PYR 2CBecca 2CJP 2CLisaB 2CLisaH 3-Benzazepines (e.g.,fenoldopam ,lorcaserin ,7-chlorolorcaserin ,SCHEMBL5334361 )3-Benzhydrylmorpholine 3-Phenylpiperidines (e.g.,3-phenylpiperidine ,3-PPP ,OSU-6162 (PNU-96391) ,LPH-5 ,LPH-48 ,Z3517967757 (Z7757) )6-AB AL-1095 Aminochromes (e.g.,adrenochrome ,adrenolutin )Benzocyclobutenes (e.g.,2CBCB-NBOMe ,bromotomscaline ,S33005 ,TCB-2 ,tomscaline )Benzoxepins (e.g.,BBOX ,IBOX ,TFMBOX )Butyltolylquinuclidine Camfetamine Cypenamine (trans -2-phenylcyclopentylamine) Diphenidine Diphenylprolinol DMBMPP Ergolines (e.g.,LSD )Fencamfamin GYKI-52895 HDMP-29 Ivabradine Methoxphenidine Methylmorphenate Milnacipran MT-45 2-Naphthylamine Org 6582 Partial ergolines (e.g.,NDTDI ,RU-27849 ,DEIMDHPCA ,DEMPDHPCA ,DEMPDHPCA-2C-D ,RU-27251 )PF-592,379 Phenylcyclopropylamines (e.g.,DMCPA ,TMT ,tranylcypromine )Phenylpiracetams (e.g.,phenylpiracetam ,MRZ-9547 ,RGPU-95 )Pyridopyrroloquinoxalines (e.g.,lumateperone ,deulumateperone ,IHCH-7079 ,IHCH-7086 ,IHCH-7113 ,ITI-1549 )Tetrahydrobenzopyranylamines (e.g.,CT-5126 )Tolazoline Tricyclics (e.g.,AMDA ,AMDH ,benzoctamine ,dizocilpine ,SpAMDA )ZC-B
Related compounds 2-Furylethylamine 2-Pyrrolylethylamine 3-Pyrrolylethylamine 3-Pyrrolylpropylamine 2-Tetrahydrofurylethylamine 4-Benzylpiperidine 7-AB Alkylamines (e.g.,1,3-DMBA Tooltip 1,3-dimethylbutylamine ,1,4-DMAA Tooltip 1,4-dimethylamylamine ,heptaminol ,iproheptine ,isometheptene ,methylhexanamine/ 1,3-DMAA ,octodrine ,oenethyl ,tuaminoheptane )Benzylamines (e.g.,benzylamine ,α-methylbenzylamine ,MDM1EA ,ALPHA ,M-ALPHA ,pargyline )Benzylpiperazines (e.g.,benzylpiperazine ,MDBZP ,fipexide )Cyclohexylaminopropanes (e.g.,propylhexedrine ,norpropylhexedrine )Cyclopentylaminopropanes (e.g.,isocyclamine ,cyclopentamine )Phenoxyethylamines (e.g.,3,4,5-trimethoxyphenoxyethylamine ,CT-4719 ,ORG-37684 )Phenylalkenylamines (e.g.,phenylbutenamine )Phenylalkynylamines (e.g.,phenylbutynamine )Phenylpiperazines (e.g.,1-phenylpiperazine ,mCPP Tooltip meta-chlorophenylpiperazine ,TFMPP Tooltip trifluoromethylphenylpiperazine ,oMPP Tooltip ortho-methylphenylpiperazine ,pFPP Tooltip para-fluorophenylpiperazine ,pMeOPP Tooltip para-methoxyphenylpiperazine )Phenylpropylamines (e.g.,phenylpropylamine ,homo-MDA ,homo-MDMA )Thienylaminopropanes (thiopropamines) (e.g.,thiopropamine ,methiopropamine ,thiothinone )
