View source for MEAI

{{Short description|Chemical compound}}
{{Drugbox
| IUPAC_name = 5-Methoxy-2-aminoindane
| image = 5-Methoxy-2-indanamine.svg
<!--Clinical data-->
| tradename = none
| pregnancy_category =
| legal_DE = NpSG
| legal_UK = PSA
| legal_status = Unscheduled
| routes_of_administration = Oral
<!--Pharmacokinetic data-->
| 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 =
<!--Identifiers-->
| 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
<!--Chemical data-->
| 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.<ref name="HalberstadtBrandtWalther2019" /> It specifically acts as a [[selective serotonin releasing agent]] (SSRA).<ref name="HalberstadtBrandtWalther2019" /> The drug is under development for the treatment of [[alcoholism]], [[cocaine use disorder]], [[metabolic syndrome]], and [[obesity]] under the developmental code name '''CMND-100'''.<ref name="AdisInsight" />
==Effects==
When used [[recreational drug|recreationally]], MEAI is reported to produce mild [[psychoactive drug|psychoactive]] effects and [[euphoriant|euphoria]].<ref name="HalberstadtBrandtWalther2019" />
==Pharmacology==
MEAI is a [[monoamine releasing agent]].<ref name="HalberstadtBrandtWalther2019">{{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 = }}</ref> It is a modestly [[binding selectivity|selective]] [[serotonin releasing agent]], with 6-fold preference for induction of [[serotonin]] release over [[norepinephrine]] release and 20-fold preference for induction of serotonin release over [[dopamine]] release.<ref name="HalberstadtBrandtWalther2019" /> In addition to inducing [[monoamine neurotransmitter]] release, MEAI has moderate [[affinity (pharmacology)|affinity]] for the [[alpha-2 adrenergic receptor|α<sub>2</sub>-adrenergic receptor]].<ref name="HalberstadtBrandtWalther2019" /> Based on these findings, MEAI might produce [[MDMA]]-like [[entactogen]]ic and [[sympathomimetic]] effects but may be expected to have reduced [[misuse liability]] in comparison.<ref name="HalberstadtBrandtWalther2019" />
==History==
MEAI appears to have been first [[chemical synthesis|synthesized]] in 1956.<ref name="HalberstadtBrandtWalther2019" />
Its molecular structure was first mentioned implicitly in a [[markush structure]] schema appearing in a patent from 1998.<ref>{{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_%26_Upjohn|Pharmacia & Upjohn Co.]]}}</ref> It was later explicitly and pharmacologically described in a peer reviewed paper in 2017 by [[David Nutt]] and Ezekiel Golan et al.<ref>{{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 | s2cid = 205304106 }}</ref> followed by another in February 2018 which detailed the [[pharmacokinetics]], [[pharmacodynamics]] and metabolism of MEAI by Shimshoni, David Nutt, Ezekiel Golan et al.<ref>{{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 | s2cid = 3879333 }}</ref> One year later it was studied and reported on in another peer reviewed paper by Halberstadt et al.<ref>{{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 α<sub>2</sub>-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 }}</ref> The aminoindane family of molecules was, perhaps, first chemically described in 1980.<ref>{{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 }}</ref><ref>{{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 }}</ref>
==Alcohol substitute==
MEAI was an early candidate of [[alcohol (drug)|alcohol]] replacement drugs that came to market during a late 2010s movement to replace alcohol with less-toxic alternatives spearheaded by British [[Psychopharmacology|psychopharmacologist]] [[David Nutt]]<ref>{{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}}</ref><ref name="pmid21036393">{{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 }}</ref><ref>{{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}}</ref> rippling to the rest of Europe.<ref>{{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}}</ref>
In an act of [[gonzo journalism]], Michael Slezak writing for [[New Scientist]], tried and reported on his experience with MEAI<ref name=":0" /> after being provided with it by Dr Zee<ref>{{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}}</ref> (Ezekiel Golan) after an interview<ref name=":0">{{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}}</ref> Golan claimed he invented MEAI and originally intended MEAI to be sold as a legal high but instead indicated plans to work with [[David Nutt]] and his company DrugScience to develop MEAI further based on Golan's patents as a "binge behaviour regulator"<ref>{{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}}</ref> and "alcoholic beverage substitute".<ref>{{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 }}</ref>
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 160mg 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.<ref>{{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  }}</ref><ref>{{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 }}</ref> In a December 2018 article by [[CBC News]], Ezekiel Golan (Dr Z/Dr Zee) was interviewed and publicly came out as the "lead scientist" of Pace claiming "tens of thousands" of bottles were already sold in Canada.<ref name = "Wright_2018">{{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}}</ref> Golan claimed the MEAI featured in Pace was "manufactured in India" and "bottled in Delaware".<ref name = "Wright_2018" /> [[Health Canada]] provided a statement to CBC News stating "Pace is an illegal and unauthorized product in Canada." Both [[Chemistry World]]<ref>{{cite web | vauthors = Extance A | date = 6 September 2017 |title=The rising tide of 'legal highs' |url=https://www.chemistryworld.com/features/the-rising-tide-of-legal-highs/3007738.article |access-date=2022-10-17 |website=Chemistry World |language=en}}</ref> and The [[BBC]] have dubbed Ezekiel Golan as "the man who invents legal highs".<ref>{{cite web |date=23 January 2018 |title=Meet Dr. Zee - the man who invented legal highs |url=https://www.bbc.co.uk/bbcthree/clip/0e5fa0a1-6305-40f9-ab11-f1fa512328fc | work = BBC }}</ref> [[The Guardian]] called him "the godfather of legal highs"<ref>{{cite web | vauthors = Jonze T |date=24 May 2016 |title=Dr Zee, the godfather of legal highs: 'I test everything on myself' |url=https://www.theguardian.com/tv-and-radio/2016/may/24/dr-zee-the-godfather-of-legal-highs-i-test-everything-on-myself |website=[[TheGuardian.com]]}}</ref> for his contribution in reintroducing [[substituted cathinone]] based drugs commonly sold as [[Bath salts (drug)]] including [[Mephedrone]]
==Pharmaceutical development==
On May 26, 2022, MEAI was prepared for [[FDA]] registration by Clearmind Medicine Inc.;<ref>{{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}}</ref><ref>{{cite web | title = Clearmind Medicine Inc. | url = https://www.thecse.com/en/listings/life-sciences/clearmind-medicine-inc | work = CSE:CMND }}</ref><ref>{{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 }}</ref> Clearmind Medicine claims wide intellectual property holdings to Ezekiel Golan's patents.<ref>{{cite patent|country=US|number=10137096|pubdate=2018-11-27|title=Binge behavior regulators|inventor = Golan E }}</ref><ref>{{cite patent|country=EP|number=3230256|pubdate=2019-11-13|title=Alcoholic beverage substitutes|inventor = Golan E }}</ref><ref>{{cite patent|country=EP|number=3230255|pubdate=2017-10-18|title=Binge behavior regulators|inventor = Golan E }}</ref><ref>{{cite web | url=https://www.clearmindmedicine.com/science-and-ip | title=The Science and IP Behind our Treatments | work = Clearmind }}</ref> In March 2022 Clearmind Medicine announced supportive evidence from animal studies in mice attesting to suppression of alcohol consumption.<ref>{{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}}</ref> In June 2022 Clearmind Medicine announced promising results from animal studies that showed promise for treating cocaine addiction with MEAI.<ref>{{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}}</ref><ref>{{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}}</ref>
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]].<ref name="AdisInsight">{{cite web | title=5-Methoxy 2-aminoindane | website=AdisInsight | date=16 October 2024 | url=https://adisinsight.springer.com/drugs/800065665 | access-date=24 October 2024}}</ref> As of October 2024, it is in the [[preclinical research|preclinical stage of development]] for these indications.<ref name="AdisInsight" />
== See also ==
* [[MMAI]]
* [[5-IAI]]
* [[MDAI]]
* [[MDMAI]]
* [[NM-2-AI]]
* [[Trifluoromethylaminoindane|TAI]]
* [[Pagoclone]]
== References ==
{{Reflist}}
== External links ==
* [https://www.drzee.org/post/late-nite-psycho-video Information Video About Alcohol Consumption]
{{Entactogens}}
{{Monoamine releasing agents}}
[[Category:2-Aminoindanes]]
[[Category:Designer drugs]]
[[Category:Entactogens and empathogens]]
[[Category:Experimental entactogens]]
[[Category:Experimental psychiatric drugs]]
[[Category:Monoamine releasing agents]]
[[Category:Phenol ethers]]