MMAI explained

5-Methoxy-6-methyl-2-aminoindane (MMAI) is a drug of the 2-aminoindane group developed in the 1990s by a team led by David E. Nichols at Purdue University.[1] It acts as a less neurotoxic and highly selective serotonin releasing agent (SSRA) and produces entactogenic effects in humans.[1] [2] [3] [4] It has been sold as a designer drug and research chemical online since 2010.

MMAI has been shown to relieve stress-induced depression in rats more robustly than sertraline,[5] and as a result it has been suggested that SSRAs like MMAI and 4-methylthioamphetamine (4-MTA) could be developed as novel antidepressants with a faster onset of therapeutic action and superior effectiveness to current antidepressants such as the selective serotonin reuptake inhibitors (SSRIs).[6]

MMAI alone does not appear to produce serotonergic neurotoxicity with either acute or chronic administration in animals.[7] [8] However, subsequent research found that a single high dose of MMAI could produce significant serotonergic neurotoxicity. In addition, combination of MMAI with the dopamine releasing agent dextroamphetamine has been found to produce dose-dependent serotonergic neurotoxicity in animals. Hence, MMAI is not a fully non-neurotoxic MDMA analogue.

Notes and References

  1. Marona-Lewicka D, Nichols DE . Behavioral effects of the highly selective serotonin releasing agent 5-methoxy-6-methyl-2-aminoindan . European Journal of Pharmacology . 258 . 1–2 . 1–13 . June 1994 . 7925587 . 10.1016/0014-2999(94)90051-5 . 10.1.1.688.1895 .
  2. Li Q, Murakami I, Stall S, Levy AD, Brownfield MS, Nichols DE, Van de Kar LD . Neuroendocrine pharmacology of three serotonin releasers: 1-(1,3-benzodioxol-5-yl)-2-(methylamino)butane (MBDB), 5-methoxy-6-methyl-2-aminoindan (MMAi) and p-methylthioamphetamine (MTA) . The Journal of Pharmacology and Experimental Therapeutics . 279 . 3 . 1261–1267 . December 1996 . 8968349 .
  3. Rudnick G, Wall SC . Non-neurotoxic amphetamine derivatives release serotonin through serotonin transporters . Molecular Pharmacology . 43 . 2 . 271–276 . February 1993 . 8429828 .
  4. Luethi D, Kolaczynska KE, Docci L, Krähenbühl S, Hoener MC, Liechti ME . Pharmacological profile of mephedrone analogs and related new psychoactive substances . Neuropharmacology . 134 . Pt A . 4–12 . May 2018 . 28755886 . 10.1016/j.neuropharm.2017.07.026 . 28786127 .
  5. Marona-Lewicka D, Nichols DE . The Effect of Selective Serotonin Releasing Agents in the Chronic Mild Stress Model of Depression in Rats . Stress . 2 . 2 . 91–100 . December 1997 . 9787258 . 10.3109/10253899709014740 .
  6. Scorza C, Silveira R, Nichols DE, Reyes-Parada M . Effects of 5-HT-releasing agents on the extracellullar hippocampal 5-HT of rats. Implications for the development of novel antidepressants with a short onset of action . Neuropharmacology . 38 . 7 . 1055–1061 . July 1999 . 10428424 . 10.1016/S0028-3908(99)00023-4 . 13714807 .
  7. Johnson MP, Nichols DE . Combined administration of a non-neurotoxic 3,4-methylenedioxymethamphetamine analogue with amphetamine produces serotonin neurotoxicity in rats . Neuropharmacology . 30 . 7 . 819–822 . July 1991 . 1717873 . 10.1016/0028-3908(91)90192-e .
  8. Johnson MP, Conarty PF, Nichols DE . [3H]monoamine releasing and uptake inhibition properties of 3,4-methylenedioxymethamphetamine and p-chloroamphetamine analogues . Eur J Pharmacol . 200 . 1 . 9–16 . July 1991 . 1685125 . 10.1016/0014-2999(91)90659-e .

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