MMAI

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

Clinical data
Other names	MMAI; MMAi; 5-Methoxy-6-methyl-2-aminoindan
Routes of administration	By mouth
Drug class	Selective serotonin releasing agent; Entactogen
ATC code	None
Legal status
Legal status	In general: uncontrolled
Identifiers
IUPAC name 5-Methoxy-6-methyl-2,3-dihydro-1H-inden-2-amine
CAS Number	136468-19-4 Y
PubChem CID	131575
ChemSpider	116274
UNII	JF10U4I82P
CompTox Dashboard (EPA)	DTXSID20927886
Chemical and physical data
Formula	C11H15NO
Molar mass	177.247 g·mol−1
3D model (JSmol)	Interactive image
SMILES Cc1cc2CC(N)Cc2cc1OC
InChI InChI=1S/C11H15NO/c1-7-3-8-4-10(12)5-9(8)6-11(7)13-2/h3,6,10H,4-5,12H2,1-2H3 Key:JLESVLCTIOAHPT-UHFFFAOYSA-N

The drug is one of the only known agents with greater than 100-fold selectivity for the serotonin transporter (SERT) over the dopamine transporter (DAT).^[5]

MMAI has been shown to relieve stress-induced depression in rats more robustly than sertraline,^[6] 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).^[7]

MMAI alone does not appear to produce serotonergic neurotoxicity with either acute or chronic administration in animals.^[8][9] However, subsequent research found that a single high dose of MMAI could produce significant serotonergic neurotoxicity.^[8][9] In addition, combination of MMAI with the dopamine releasing agent dextroamphetamine has been found to produce dose-dependent serotonergic neurotoxicity in animals.^[8] Hence, MMAI is not a fully non-neurotoxic MDMA analogue.^[8][9]

References

1. Marona-Lewicka D, Nichols DE (June 1994). "Behavioral effects of the highly selective serotonin releasing agent 5-methoxy-6-methyl-2-aminoindan". European Journal of Pharmacology. 258 (1–2): 1–13. CiteSeerX 10.1.1.688.1895. doi:10.1016/0014-2999(94)90051-5. PMID 7925587.
2. Li Q, Murakami I, Stall S, Levy AD, Brownfield MS, Nichols DE, Van de Kar LD (December 1996). "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. PMID 8968349.
3. Rudnick G, Wall SC (February 1993). "Non-neurotoxic amphetamine derivatives release serotonin through serotonin transporters". Molecular Pharmacology. 43 (2): 271–276. PMID 8429828.
4. Luethi D, Kolaczynska KE, Docci L, Krähenbühl S, Hoener MC, Liechti ME (May 2018). "Pharmacological profile of mephedrone analogs and related new psychoactive substances" (PDF). Neuropharmacology. 134 (Pt A): 4–12. doi:10.1016/j.neuropharm.2017.07.026. PMID 28755886. S2CID 28786127.
5. Rudin D, Liechti ME, Luethi D (September 2021). "Molecular and clinical aspects of potential neurotoxicity induced by new psychoactive stimulants and psychedelics". Exp Neurol. 343: 113778. doi:10.1016/j.expneurol.2021.113778. PMID 34090893.
6. Marona-Lewicka D, Nichols DE (December 1997). "The Effect of Selective Serotonin Releasing Agents in the Chronic Mild Stress Model of Depression in Rats". Stress. 2 (2): 91–100. doi:10.3109/10253899709014740. PMID 9787258.
7. Scorza C, Silveira R, Nichols DE, Reyes-Parada M (July 1999). "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. doi:10.1016/S0028-3908(99)00023-4. PMID 10428424. S2CID 13714807.
8. Johnson MP, Nichols DE (July 1991). "Combined administration of a non-neurotoxic 3,4-methylenedioxymethamphetamine analogue with amphetamine produces serotonin neurotoxicity in rats". Neuropharmacology. 30 (7): 819–822. doi:10.1016/0028-3908(91)90192-e. PMID 1717873.
9. Johnson MP, Conarty PF, Nichols DE (July 1991). "[3H]monoamine releasing and uptake inhibition properties of 3,4-methylenedioxymethamphetamine and p-chloroamphetamine analogues". Eur J Pharmacol. 200 (1): 9–16. doi:10.1016/0014-2999(91)90659-e. PMID 1685125.