Abstract—The effect of RS‐8359, (±)‐4‐(4‐cyanophenyl)amino‐6,7‐dihydro‐7‐hydroxy‐5H‐cyclopentad‐pyrimidine on monoamine oxidase (MAO) has been compared with a hydrazinic MAO inhibitor, safrazine (β‐piperonylisopropylhydrazine hydrochloride,) which is a MAO inhibitor used clinically. In‐vitro radiochemical determination of MAO activity showed that the IC50 of RS‐8359 was 0·52 μM for the deamination of 5‐hydroxytryptamine (5‐HT) in the mouse brain mitochondrial preparation, while β‐phenylethylamine (PEA) deamination was inhibited by only 20 at 100 μM of the drug. 5‐HT deamination in the brain homogenate prepared from mice killed 60 min after administration of RS‐8359 was inhibited significantly by 14 and 48, at 30 and 100 mg kg−1(p.o.), respectively, while deamination of PEA was little affected at the same doses. On the other hand, safrazine strongly inhibited both 5‐HT and PEA deaminations, but showed no selectivity toward the substrate used. The extent of MAO inhibition by RS‐8359, measured fluorometrically with kynuramine as a substrate in the brain homogenate, was independent of preincubation up to 80 min. In contrast, the inhibitory potency of safrazine was strengthened by preincubation in a time‐dependent manner. Oral administration of RS‐8359 (3‐30 mg kg−1) caused a dose‐dependent increase in endogenous monoamines in mouse brain, which disappeared a few hours after its administration. Increase in monoamine content caused by safrazine lasted for at least 24 h. These results indicate that RS‐8359 is a reversible and specific inhibitor of MAO‐A, while safrazine is an irreversible an
展开▼
