Monoamine Oxidase Inhibitory Properties of Optical Isomers and N-substituted Derivatives of 4-methylthioamphetamine
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(6)-4-Methylthioamphetamine (MTA) was resolved into its enantiomers, and a series of N-alkyl derivatives of the parent compound, as well as its a-ethyl analogue, were prepared. The monoamine oxidase (MAO) inhibitory properties of these substances were evaluated in vitro, using a crude rat brain mitochondrial suspension as the source of enzyme. All compounds produced a selective, reversible and concentration-related inhibition of MAO-A. (1)-MTA proved to be the most potent inhibitor studied, while all the other derivatives were less active than the parent compound, with (2)-MTA being about 18 times less potent than the (1) isomer. The analysis of structure–activity relationships indicates that the introduction of alkyl substituents on the amino group of MTA leads to a reduction in the potency of the derivatives as MAO-A inhibitors, an effect which increases with the size of the substituent.
This work was supported by the Presidential Chair in Science (BKC, 1996), ICM grant N8 P99-031-F, FONDECYT grant N8 1000776 and DICYT grant N8 029901RP.
Quote ItemJournal of Enzyme Inhibition and Medicinal Chemistry, Vol. 18 (4), p. 339–347, 2003