4-MTMA is known to act as a potentserotonin releasing agent (SRA).[1][3] Its EC50Tooltip half-maximal effective concentration value for induction of serotonin release in rat brain synaptosomes was 21nM, whereas norepinephrine and dopamine release were not reported.[3] In addition to its MRA activity, like 4-MTA, the drug has been found to act as a potent reversibleenzyme inhibitor of monoamine oxidase A (MAO-A).[4][5][6] It is about one-third as potent as 4-MTA as an MAO-A inhibitor.[5][6] Its IC50Tooltip half-maximal inhibitory concentration value for MAO-A inhibition is 0.89nM, whereas the values of 4-MTA are 0.13nM for (+)-4-MTA and 2.04nM for (–)-4-MTA.[5][6] Neither 4-MTA nor 4-MTMA inhibited monoamine oxidase B (MAO-B).[5][6] Potent monoamine oxidase inhibition by amphetamines has been associated with dangerous and sometimes fatal toxicity in humans.[5][6]
^ abcMurphy J, Flynn JJ, Cannon DM, Guiry PJ, McCormack P, Baird AW, et al. (May 2002). "In vitro neuronal and vascular responses to 5-hydroxytryptamine: modulation by 4-methylthioamphetamine, 4-methylthiomethamphetamine and 3,4-methylenedioxymethamphetamine". Eur J Pharmacol. 444 (1–2): 61–67. doi:10.1016/s0014-2999(02)01586-8. PMID12191583.
^ abcdefgKhorana N, Pullagurla MR, Dukat M, Young R, Glennon RA (August 2004). "Stimulus effects of three sulfur-containing psychoactive agents". Pharmacol Biochem Behav. 78 (4): 821–826. doi:10.1016/j.pbb.2004.05.021. PMID15301941. The present investigation examined these agents, and the N-monomethyl analog of 4-MTA (i.e., 4-MTMA), in tests of stimulus generalization (substitution) using a two-lever drug discrimination task with groups of rats trained to discriminate either the hallucinogen DOM [1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane], the stimulant cocaine, or the empathogen MDMA from vehicle. 4-MTA and its N-monomethyl analog 4-MTMA (ED50 = 0.8 mg/kg in both cases) substituted only for the MDMA stimulus, whereas 2C-T-7 (ED50 = 0.8 mg/kg) substituted only for the DOM stimulus. Thus, at the doses examined, 4-MTA and 4-MTMA appear to be MDMA-like agents, and 2C-T-7 seems best classified as a DOM-like hallucinogen.
^ abcdefgBłachut D, Wojtasiewicz K, Czarnocki Z, Szukalski B (November 2009). "The analytical profile of some 4-methylthioamphetamine (4-MTA) homologues". Forensic Sci Int. 192 (1–3): 98–114. doi:10.1016/j.forsciint.2009.08.009. PMID19766415. Whereas pharmacological properties of 4-MTA are well described in the literature, much less is known about its N-methylated homologue, 4-methylthiomethamphetamine (4- MTMA). The 4-MTMA has been examined in the test of stimulus generalization using MDMA and PMMA-trained rats [11,12]. Because the stimulus generalization failed to occur with PMMA and instead the substitution took place upon the administration of 4-MTMA to MDMA-trained animals, the drug was considered to be a MDMA-like agent. Only one study was devoted to the biological activity of N-alkyl derivatives of 4-MTA with substituents other than N-methyl [16]. An important conclusion of this work was that all derivatives investigated, including 4-MTA and its N-methyl, Nethyl, N-propyl and N,N-dimethyl-homologues, acted as selective, reversible inhibitors of MAO-A and their potency decreased with the increasing size of the N-alkyl chain.
^ abcdeReyes-Parada M, Iturriaga-Vasquez P, Cassels BK (2019). "Amphetamine Derivatives as Monoamine Oxidase Inhibitors". Front Pharmacol. 10 1590. doi:10.3389/fphar.2019.01590. PMC6989591. PMID32038257. Relatively few amino group substituents have been studied in AMPH derivatives regarding their influence upon MAOI potency. In general terms, any N-substitution leads to a decrease in the activity of the compound as a MAOI-A. Thus, the N-methyl derivatives of AMPH, MTA, p-methoxyAMPH (PMA), and 3,4-methylenedioxyAMPH (MDA)— i.e. methamphetamine, NMMTA, PMMA, and MDMA respectively— have about one-third the inhibitory potency of their corresponding primary amine congeners (Scorza et al., 1997; Hurtado-Guzmán et al., 2003; Matsumoto et al., 2014; Santillo, 2014; Tables 1, 2, 4).
^ abcDukat M, Young R, Glennon RA (May 2002). "Effect of PMA optical isomers and 4-MTA in PMMA-trained rats". Pharmacol Biochem Behav. 72 (1–2): 299–305. doi:10.1016/s0091-3057(01)00776-6. PMID11900800.
