4-Methylthiomethamphetamine

4-Methylthiomethamphetamine (4-MTMA; code name PAL-1063), also known as N-methyl-4-methylthioamphetamine (NMMTA), is a monoamine releasing agent (MRA) of the amphetamine family related to 4-methylthioamphetamine (4-MTA) and N,N-dimethyl-4-methylthioamphetamine (DMMTA or 4-MTDMA). Much less is known about 4-MTMA compared to 4-MTA.

4-MTMA is known to act as a potent serotonin releasing agent (SRA). Its EC₅₀Tooltip half-maximal effective concentration value for induction of serotonin release in rat brain synaptosomes was 21 nM, whereas norepinephrine and dopamine release were not reported. In addition to its MRA activity, like 4-MTA, the drug has been found to act as a potent reversible enzyme inhibitor of monoamine oxidase A (MAO-A). It is about one-third as potent as 4-MTA as an MAO-A inhibitor. Its IC₅₀Tooltip half-maximal inhibitory concentration value for MAO-A inhibition is 0.89 nM, whereas the values of 4-MTA are 0.13 nM for (+)-4-MTA and 2.04 nM for (–)-4-MTA. Neither 4-MTA nor 4-MTMA inhibited monoamine oxidase B (MAO-B). Potent monoamine oxidase inhibition by amphetamines has been associated with dangerous and sometimes fatal toxicity in humans.

In animal drug discrimination tests, 4-MTA and 4-MTMA were found to generalize to MDMA. 4-MTA substituted for the serotonergic agent PMMA, whereas 4-MTMA did not. 4-MTA did not substitute for the serotonergic psychedelic DOM, whereas 4-MTMA was not assessed in DOM-trained animals. Neither 4-MTA nor 4-MTMA substituted for the psychostimulants dextroamphetamine or cocaine. It was concluded that 4-MTA and 4-MTMA show mainly MDMA-like effects in rodents.

4-MTMA had not been identified as an illicit drug or drug of misuse by 2004. However, it is said to have been encountered as a novel designer drug by 2015.