Monoamine oxidase inhibitory properties of optical isomers and N-substituted derivatives of 4-methylthioamphetamine.
(+/-)-4-Methylthioamphetamine (MTA) was resolved into its enantiomers, and a series of N-alkyl derivatives of the parent compound, as well as its alpha-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. (+)-MTA proved to be the most potent inhibitor studied, while all the other derivatives were less active than the parent compound, with (-)-MTA being about 18 times less potent than the (+) 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.
Chemistry Department, Faculty of Sciences, University of Chile, Chile.
Claudio
C
Hurtado-Guzmán
Angelica
A
Fierro
Patricio
P
Iturriaga-Vásquez
Silvia
S
Sepúlveda-Boza
Bruce K
BK
Cassels
Miguel
M
Reyes-Parada
D000662:Amphetamines / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D008995:Monoamine Oxidase / Q000737:chemistry; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000662:Amphetamines; D008996:Monoamine Oxidase Inhibitors; C078956:4-methylthioamphetamine; D008995:Monoamine Oxidase