MEAI
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MEAI, also known as 5-methoxy-2-aminoindane (5-MeO-AI), is a monoamine releasing agent of the 2-aminoindane group.[1] It specifically acts as a selective serotonin releasing agent (SSRA).[1] The drug is under development for the treatment of alcoholism, cocaine use disorder, metabolic syndrome, and obesity under the developmental code name CMND-100.[2]
Effects
When used recreationally, MEAI is reported to produce mild psychoactive effects and euphoria.[1]
Pharmacology
Pharmacodynamics
MEAI is a monoamine releasing agent (MRA).[1] 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.[1] In addition to inducing monoamine neurotransmitter release, MEAI has moderate affinity for the α2-adrenergic receptor.[1] Based on these findings, MEAI might produce MDMA-like entactogenic and sympathomimetic effects but may be expected to have reduced misuse liability in comparison.[1]
| Compound | Monoamine release (EC50, nM) | Ref | ||
|---|---|---|---|---|
| Serotonin | Norepinephrine | Dopamine | ||
| 2-AI | >10,000 | 86 | 439 | [1] |
| MDAI | 114 | 117 | 1,334 | [1] |
| MMAI | 31 | 3,101 | >10,000 | [1] |
| MEAI | 134 | 861 | 2,646 | [1] |
| d-Amphetamine | 698–1,765 | 6.6–7.2 | 5.8–24.8 | [3][4][5][6][7] |
| MDA | 160–162 | 47–108 | 106–190 | [8][5][9] |
| MDMA | 50–85 | 54–110 | 51–278 | [3][10][11][8][9] |
| 3-MA | ND | 58.0 | 103 | [5] |
| 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: [1] | ||||
Chemistry
MEAI, also known as 5-methoxy-2-aminoindane, is a 2-aminoindane derivative.[12] It is the 2-aminoindane analogue of the amphetamine 3-methoxyamphetamine.[12]
History
MEAI appears to have been first synthesized in 1956.[1] Its molecular structure was first mentioned implicitly in a markush structure schema appearing in a patent from 1998.[13] It was later explicitly and pharmacologically described in a peer reviewed paper in 2017 by David Nutt and Ezekiel Golan et al.[14] followed by another in February 2018 which detailed the pharmacokinetics, pharmacodynamics and metabolism of MEAI by Shimshoni, David Nutt, Ezekiel Golan et al.[15] One year later it was studied and reported on in another peer reviewed paper by Halberstadt et al.[16] The aminoindane family of molecules was, perhaps, first chemically described in 1980.[17][18]
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[19][20][21] rippling to the rest of Europe.[22]
In an act of gonzo journalism, Michael Slezak writing for New Scientist, tried and reported on his experience with MEAI[23] after being provided with it by Dr Zee (Ezekiel Golan)[24] following an interview.[23] 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 DrugScience. The goal was to develop MEAI further based on Golan's patents as a "binge behaviour regulator"[25] and "alcoholic beverage substitute".[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 after Health Canada released a warning indicating the substance was considered illegal to market for consumption in Canada due to structural similarity to amphetamine.[27][28] 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.[29] Golan claimed the MEAI featured in Pace was "manufactured in India" and "bottled in Delaware".[29] 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 Clearmind Medicine Inc.;[30][31][32] Clearmind Medicine claims wide intellectual property holdings to Ezekiel Golan's patents.[33][34][35][36] In March 2022 Clearmind Medicine announced supportive evidence from animal studies in mice attesting to suppression of alcohol consumption.[37] In June 2022 Clearmind Medicine announced promising results from animal studies that showed promise for treating cocaine addiction with MEAI.[38][39]
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.[2] As of October 2024, it is in the preclinical stage of development for these indications.[2]
See also
References
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- ↑ <templatestyles src="Citation/styles.css"/>Template:Citation/make link, 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 Script error: No such module "auto date formatter"., assigned to Pharmacia & Upjohn Co.Script error: No such module "Check for unknown parameters".
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- ↑ <templatestyles src="Citation/styles.css"/>Template:Citation/make link, Golan E, "Alcoholic beverage substitutes", issued Script error: No such module "auto date formatter".Script error: No such module "Check for unknown parameters".
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- ↑ <templatestyles src="Citation/styles.css"/>Template:Citation/make link, Golan E, "Binge behavior regulators", published Script error: No such module "auto date formatter".Script error: No such module "Check for unknown parameters".
- ↑ <templatestyles src="Citation/styles.css"/>Template:Citation/make link, Golan E, "Alcoholic beverage substitutes", published Script error: No such module "auto date formatter".Script error: No such module "Check for unknown parameters".
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External links
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