:MEAI

{{Infobox drug

| IUPAC_name = 5-Methoxy-2-aminoindane

| image = 5-Methoxy-2-indanamine.svg

| tradename = none

| pregnancy_category =

| legal_DE = NpSG

| legal_UK = PSA

| legal_status = Unscheduled

| routes_of_administration = Oral

| bioavailability = High{{Citation needed|date=October 2024}}

| protein_bound =

| metabolism = Acetyl-aminoindandane{{Citation needed|date=October 2024}}

| elimination_half-life = Non-linear{{Citation needed|date=October 2024}}

| excretion =

| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 73305-09-6

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = AD8S15863A

| ATC_prefix =

| ATC_suffix =

| PubChem = 12147687

| ChemSpiderID = 11591017

| synonyms = 5-MeO-AI; 5-MeO-2-AI; 5-Methoxy-2-aminoindane; 5-Methoxy-2-aminoindan; Chaperon; CMND-100; CMND100

| C=10|H=13|N=1|O=1

| SMILES = COC1=CC2=C(CC(C2)N)C=C1

| StdInChI = 1S/C10H13NO/c1-12-10-3-2-7-4-9(11)5-8(7)6-10/h2-3,6,9H,4-5,11H2,1H3

| StdInChIKey = HLXHCNWEVQNNKA-UHFFFAOYSA-N

}}

MEAI, also known as 5-methoxy-2-aminoindane (5-MeO-AI), is a monoamine releasing agent of the 2-aminoindane group. It specifically acts as a selective serotonin releasing agent (SSRA). The drug is under development for the treatment of alcoholism, cocaine use disorder, metabolic syndrome, and obesity under the developmental code name CMND-100.

Effects

When used recreationally, MEAI is reported to produce mild psychoactive effects and euphoria.

Pharmacology

=Pharmacodynamics=

MEAI is a monoamine releasing agent (MRA).{{cite journal | vauthors = Halberstadt AL, Brandt SD, Walther D, Baumann MH | title = 2-Aminoindan and its ring-substituted derivatives interact with plasma membrane monoamine transporters and α2-adrenergic receptors | journal = Psychopharmacology (Berl) | volume = 236 | issue = 3 | pages = 989–999 | date = March 2019 | pmid = 30904940 | pmc = 6848746 | doi = 10.1007/s00213-019-05207-1 | url = }} It is a modestly selective serotonin releasing agent (SSRA), with 6-fold preference for induction of serotonin release over norepinephrine release and 20-fold preference for induction of serotonin release over dopamine release. In addition to inducing monoamine neurotransmitter release, MEAI has moderate affinity for the α₂-adrenergic receptor. Based on these findings, MEAI might produce MDMA-like entactogenic and sympathomimetic effects but may be expected to have reduced misuse liability in comparison.

rowspan="2" \| Compound	colspan="3" \| Monoamine release ({{Abbrlink\|EC₅₀\|half-maximal effective concentration}}, nM) \|\| rowspan="2" \| Ref
class="wikitable" style="font-size:small;" \|+ {{Nowrap\|Activities of 2-aminoindanes and amphetamine relatives}}
Serotonin	Norepinephrine	Dopamine
2-AI	>10,000	86	439
MDAI	114	117	1,334
MMAI	31	3,101	>10,000
MEAI	134	861	2,646
d-Amphetamine	698–1,765	6.6–7.2	5.8–24.8	{{cite journal \| vauthors = 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 \| title = Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products \| journal = Neuropsychopharmacology \| volume = 38 \| issue = 4 \| pages = 552–562 \| date = March 2013 \| pmid = 23072836 \| pmc = 3572453 \| doi = 10.1038/npp.2012.204 }}{{cite book \| vauthors = Blough B \| chapter = Dopamine-releasing agents \| veditors = Trudell ML, Izenwasser S \| title = Dopamine Transporters: Chemistry, Biology and Pharmacology \| pages = 305–320 \| date = July 2008 \| isbn = 978-0-470-11790-3 \| oclc = 181862653 \| ol = OL18589888W \| publisher = Wiley \| location = Hoboken [NJ] \| doi = \| url = https://books.google.com/books?id=QCagLAAACAAJ \| chapter-url = https://bitnest.netfirms.com/external/Books/Dopamine-releasing-agents_c11.pdf }}{{cite book \| vauthors = Glennon RA, Dukat M \| title = Neuropharmacology of New Psychoactive Substances (NPS) \| chapter = Structure-Activity Relationships of Synthetic Cathinones \| series = Current Topics in Behavioral Neurosciences \| volume = 32 \| pages = 19–47 \| date = 2017 \| pmid = 27830576 \| pmc = 5818155 \| doi = 10.1007/7854_2016_41 \| isbn = 978-3-319-52442-9 \| chapter-url = }}{{cite book \| vauthors = Partilla JS, Dersch CM, Baumann MH, Carroll FI, Rothman RB \| chapter = Profiling CNS Stimulants with a High-Throughput Assay for Biogenic Amine Transporter Substractes \| title = Problems of Drug Dependence 1999: Proceedings of the 61st Annual Scientific Meeting, The College on Problems of Drug Dependence, Inc \| series = NIDA Res Monogr \| volume = 180 \| pages = 1–476 (252) \| date = 1999 \| pmid = 11680410 \| doi = \| url = https://archives.nida.nih.gov/sites/default/files/180.pdf#page=261 \| quote = 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). [...] }}
MDA	160–162	47–108	106–190
MDMA	50–85	54–110	51–278	{{cite journal \| vauthors = Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS \| title = Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin \| journal = Synapse \| volume = 39 \| issue = 1 \| pages = 32–41 \| date = January 2001 \| pmid = 11071707 \| doi = 10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3 \| s2cid = 15573624 }}{{cite journal \| vauthors = Baumann MH, Ayestas MA, Partilla JS, Sink JR, Shulgin AT, Daley PF, Brandt SD, Rothman RB, Ruoho AE, Cozzi NV \| title = The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue \| journal = Neuropsychopharmacology \| volume = 37 \| issue = 5 \| pages = 1192–1203 \| date = April 2012 \| pmid = 22169943 \| pmc = 3306880 \| doi = 10.1038/npp.2011.304 }}{{cite journal \| vauthors = Marusich JA, Antonazzo KR, Blough BE, Brandt SD, Kavanagh PV, Partilla JS, Baumann MH \| title = The new psychoactive substances 5-(2-aminopropyl)indole (5-IT) and 6-(2-aminopropyl)indole (6-IT) interact with monoamine transporters in brain tissue \| journal = Neuropharmacology \| volume = 101 \| pages = 68–75 \| date = February 2016 \| pmid = 26362361 \| pmc = 4681602 \| doi = 10.1016/j.neuropharm.2015.09.004 }}{{cite journal \| vauthors = Setola V, Hufeisen SJ, Grande-Allen KJ, Vesely I, Glennon RA, Blough B, Rothman RB, Roth BL \| title = 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") induces fenfluramine-like proliferative actions on human cardiac valvular interstitial cells in vitro \| journal = Molecular Pharmacology \| volume = 63 \| issue = 6 \| pages = 1223–1229 \| date = June 2003 \| pmid = 12761331 \| doi = 10.1124/mol.63.6.1223 \| s2cid = 839426 }}{{cite journal \| vauthors = Brandt SD, Walters HM, Partilla JS, Blough BE, Kavanagh PV, Baumann MH \| title = The psychoactive aminoalkylbenzofuran derivatives, 5-APB and 6-APB, mimic the effects of 3,4-methylenedioxyamphetamine (MDA) on monoamine transmission in male rats \| journal = Psychopharmacology (Berl) \| volume = 237 \| issue = 12 \| pages = 3703–3714 \| date = December 2020 \| pmid = 32875347 \| doi = 10.1007/s00213-020-05648-z \| url = \| pmc = 7686291 }}
3-MA	{{Abbr\|ND\|No data}}	58.0	103
class="sortbottom" \| colspan="5" style="width: 1px; background-color:#eaecf0; text-align: center;" \| Notes: The smaller the value, the more strongly the compound produces the effect. The assays were done in rat brain synaptosomes and human potencies may be different. See also Monoamine releasing agent § Activity profiles for a larger table with more compounds. Refs:

Chemistry

MEAI, also known as 5-methoxy-2-aminoindane, is a 2-aminoindane derivative. It is the 2-aminoindane analogue of the amphetamine 3-methoxyamphetamine.{{cite journal | vauthors = Nichols DE, Marona-Lewicka D, Huang X, Johnson MP | title = Novel serotonergic agents | journal = Drug des Discov | volume = 9 | issue = 3–4 | pages = 299–312 | date = 1993 | pmid = 8400010 | doi = | url = https://bitnest.netfirms.com/external/DrugDes.Disc/9.299 }}

History

MEAI appears to have been first synthesized in 1956.

Its molecular structure was first mentioned implicitly in a markush structure schema appearing in a patent from 1998.{{cite patent|country=US|number=5708018|title=2-aminoindans as selective dopamine D3 ligands|pubdate=1998-01-13|inventor= Haadsma-Svensson SR, Andersson BR, Sonesson CA, Lin CH, Waters RN, Svensson KA, Carlsson PA, Hansson LO, Stjernlof NP |assign1=Pharmacia & Upjohn Co.}} It was later explicitly and pharmacologically described in a peer reviewed paper in 2017 by David Nutt and Ezekiel Golan et al.{{cite journal | vauthors = Shimshoni JA, Winkler I, Edery N, Golan E, van Wettum R, Nutt D | title = Toxicological evaluation of 5-methoxy-2-aminoindane (MEAI): Binge mitigating agent in development | journal = Toxicology and Applied Pharmacology | volume = 319 | pages = 59–68 | date = March 2017 | pmid = 28167221 | doi = 10.1016/j.taap.2017.01.018 | bibcode = 2017ToxAP.319...59S | s2cid = 205304106 }} followed by another in February 2018 which detailed the pharmacokinetics, pharmacodynamics and metabolism of MEAI by Shimshoni, David Nutt, Ezekiel Golan et al.{{cite journal | vauthors = Shimshoni JA, Sobol E, Golan E, Ben Ari Y, Gal O | title = Pharmacokinetic and pharmacodynamic evaluation of 5-methoxy-2-aminoindane (MEAI): A new binge-mitigating agent | journal = Toxicology and Applied Pharmacology | volume = 343 | pages = 29–39 | date = March 2018 | pmid = 29458138 | doi = 10.1016/j.taap.2018.02.009 | bibcode = 2018ToxAP.343...29S | s2cid = 3879333 }} One year later it was studied and reported on in another peer reviewed paper by Halberstadt et al.{{cite journal | vauthors = Halberstadt AL, Brandt SD, Walther D, Baumann MH | title = 2-Aminoindan and its ring-substituted derivatives interact with plasma membrane monoamine transporters and α₂-adrenergic receptors | journal = Psychopharmacology | volume = 236 | issue = 3 | pages = 989–999 | date = March 2019 | pmid = 30904940 | pmc = 6848746 | doi = 10.1007/s00213-019-05207-1 }} The aminoindane family of molecules was, perhaps, first chemically described in 1980.{{cite journal | vauthors = Sainsbury PD, Kicman AT, Archer RP, King LA, Braithwaite RA | title = Aminoindanes--the next wave of 'legal highs'? | journal = Drug Testing and Analysis | volume = 3 | issue = 7–8 | pages = 479–482 | year = 2011 | pmid = 21748859 | doi = 10.1002/dta.318 }}{{cite journal | vauthors = Cannon JG, Perez JA, Pease JP, Long JP, Flynn JR, Rusterholz DB, Dryer SE | title = Comparison of biological effects of N-alkylated congeners of beta-phenethylamine derived from 2-aminotetralin, 2-aminoindan, and 6-aminobenzocycloheptene | journal = Journal of Medicinal Chemistry | volume = 23 | issue = 7 | pages = 745–749 | date = July 1980 | pmid = 7190613 | doi = 10.1021/jm00181a009 }}

Alcohol substitute

MEAI was an early candidate of alcohol replacement drugs that came to market during a late 2010s movement to replace alcohol with less-toxic alternatives spearheaded by British psychopharmacologist David Nutt{{cite web | vauthors = Nutt D | title = Decision making about illegal drugs: time for science to take the lead | work = Nobel Forum, Karolinska Institutet | date = 23 October 2013 | via=YouTube |url=https://www.youtube.com/watch?v=mDo09IBVHZw |language=en}}{{cite journal | vauthors = Nutt DJ, King LA, Phillips LD | title = Drug harms in the UK: a multicriteria decision analysis | journal = Lancet | location = London, England | volume = 376 | issue = 9752 | pages = 1558–65 | date = November 2010 | pmid = 21036393 | doi = 10.1016/S0140-6736(10)61462-6 | s2cid = 5667719 }}{{cite news | vauthors = Forster K |title=Hangover free alcohol is finally here |url=https://www.independent.co.uk/life-style/health-and-families/health-news/hangover-free-alcohol-david-nutt-alcosynth-nhs-postive-effects-benzodiazepine-guy-bentley-a7324076.html |access-date=25 March 2022 |work=The Independent |date=24 September 2016 |language=en}} rippling to the rest of Europe.{{cite web |title=Rauschmittel und gesellschaftliche Probleme | trans-title = Drug related societal issues |url=https://benedictwermter.com/gesellschaftliche-probleme-und-rauschmittel-drug-related-societal-issues/ |website=Benedict Wermter | vauthors = Wermter B |language=de-DE |date=29 April 2019}}

In an act of gonzo journalism, Michael Slezak writing for New Scientist, tried and reported on his experience with MEAI after being provided with it by Dr Zee (Ezekiel Golan){{cite news | vauthors = Slezak M |date=9 August 2014 |title= An Interview with Dr Z |pages=1–3 |work=New Scientist |url= https://www.drzee.org/_files/ugd/7ca39c_857476e79f6947d3befecdd31deaa83f.pdf |access-date=16 October 2022}} following an interview.{{cite web | vauthors = Slezak M |date=30 December 2014 |title=High and dry? Party drug could target excess drinking |url=https://www.newscientist.com/article/mg22530022-900-high-and-dry-party-drug-could-target-excess-drinking/ |access-date=2022-10-16 |website=New Scientist |language=en-US}} Golan claimed that he invented MEAI and originally intended for it to be sold as a legal high but changed his mind, indicating plans to work with Nutt and his company [https://www.drugscience.org.uk/ DrugScience]. The goal was to develop MEAI further based on Golan's patents as a "binge behaviour regulator"{{cite patent | country = US |number= 10406123B2|title=Binge behavior regulators|gdate=2019-09-10|inventor= Golan E |url=https://patents.google.com/patent/US10406123B2/en}} and "alcoholic beverage substitute".{{cite patent | country = US |number= 20170360067 |title=Alcoholic beverage substitutes |gdate=2017-12-21 |inventor = Golan E |url= https://patents.google.com/patent/US20170360067A1/en?q=golan+alcoholic+beverage+substitutes&oq=golan+alcoholic+beverage+substitutes }}

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 after Health Canada released a warning indicating the substance was considered illegal to market for consumption in Canada due to structural similarity to amphetamine.{{cite web | url=https://www.newswire.ca/news-releases/advisory---health-canada-warns-consumers-that-pace-promoted-as-an-alcohol-substitute--is-unauthorized-and-may-pose-serious-health-risks-703346102.html | title=Advisory - Health Canada warns consumers that Pace, promoted as an alcohol substitute, is unauthorized and may pose serious health risks | work = Health Canada | via = CISION | date = 21 December 2018 }}{{cite web | vauthors = Brunet J | date = 24 April 2019 | url=https://www.thewalrus-factchecking.com/post/fact-check-is-pace-an-alcohol-alternative-legal-in-canada | title=FACT CHECK: Is Pace, an "Alcohol Alternative," Legal in Canada? | work = The Walrus | location = Toronto, Ontario }} In a December 2018 article by 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.{{cite news | vauthors = Wright J |date=8 December 2018 |title=Is this drink really a new 'alcohol alternative'? |pages=All |work=Information Morning Saint John |url=https://www.cbc.ca/news/canada/new-brunswick/pace-drink-alcohol-alternative-binge-drinking-canada-1.4933533 |access-date=15 October 2022}} Golan claimed the MEAI featured in Pace was "manufactured in India" and "bottled in Delaware". Health Canada provided a statement to CBC News stating "Pace is an illegal and unauthorized product in Canada."

Pharmaceutical development

On May 26, 2022, MEAI was prepared for FDA registration by [https://www.clearmindmedicine.com/ Clearmind Medicine Inc.];{{cite web |title=Clearmind Medicine |url=https://www.clearmindmedicine.com/news-release/clearmind-announces-successful-pre-ind-meeting-with-u-s-fda-for-cmnd-100-for-alcohol-use-disorder |website=www.clearmindmedicine.com}}{{cite web | title = Clearmind Medicine Inc. | url = https://www.thecse.com/en/listings/life-sciences/clearmind-medicine-inc | work = CSE:CMND }}{{cite news | url = https://www.globes.co.il/news/article.aspx?did=1001402418 | title = החברה שמנסה להפוך סם פסיכדלי למוצר נגד התמכרות | trans-title = The company trying to turn a psychedelic drug into an anti-addiction product | work = Globes | date = 16 February 2022 | language = Hebrew | last1 = וינרב | first1 = גלי }} Clearmind Medicine claims wide intellectual property holdings to Ezekiel Golan's patents.{{cite patent|country=US|number=10137096|pubdate=2018-11-27|title=Binge behavior regulators|inventor = Golan E }}{{cite patent|country=EP|number=3230256|pubdate=2019-11-13|title=Alcoholic beverage substitutes|inventor = Golan E }}{{cite patent|country=EP|number=3230255|pubdate=2017-10-18|title=Binge behavior regulators|inventor = Golan E }}{{cite web | url=https://www.clearmindmedicine.com/science-and-ip | title=The Science and IP Behind our Treatments | work = Clearmind }} In March 2022 Clearmind Medicine announced supportive evidence from animal studies in mice attesting to suppression of alcohol consumption.{{cite web |title=Clearmind Medicine |url=https://www.clearmindmedicine.com/news-release/clearmind-medicine-announces-positive-results-on-cmnd-100-trials |website=www.clearmindmedicine.com}} In June 2022 Clearmind Medicine announced promising results from animal studies that showed promise for treating cocaine addiction with MEAI.{{cite web |title=Clearmind Medicine |url=https://www.clearmindmedicine.com/news-release/clearmind-medicine-announces-positive-pre-clinical-results-for-cocaine-addiction-treatment |website=www.clearmindmedicine.com |access-date=14 August 2022}}{{cite web |title=Clearmind Medicine |url=https://www.clearmindmedicine.com/news-release/clearmind-medicine-announces-additional-positive-pre-clinical-results-for-its-cocaine-addiction-treatment |access-date=2022-10-16 |website=www.clearmindmedicine.com}}

MEAI, under the developmental code name CMND-100, is under development by Clearmind Medicine for the treatment of alcoholism, cocaine use disorder, metabolic syndrome, and obesity.{{cite web |date=16 December 2024 |title=Revolutionary Psychedelics for Treating Addiction & Mental Health |url=https://www.clearmindmedicine.com/news-release/clearmind-medicine-announces-irb-approval-for-fda-first-in-human-clinical-trial-of-cmnd-100-at-second-clinical-site |access-date=16 March 2025 |website=Clearmind}} As of October 2024, it is in the preclinical stage of development for these indications.