Oxidation of 1-amino-4-phenyl-1,2,3,6-tetrahydropyridine, a 1-amino analogof MPTP, by type A and B monoamine oxidase

A l-amino analog of MPTP, 1(N)-amino-4-phenyl-1,2,3,6-tetrahydropyridine. w as synthesized and the oxidation was examined using human synaptosomal mito chondria as sources of type A and B monoamine oxidase. An oxidation product , 1-amino-4-phenylpyridinium ion, was quantified by high-performance liquid chromatography-fluorometric detection. The amino analog was a substrate of both type A and B monoamine oxidase and the oxidation depended linearly on the enzyme amount and the reaction time with an optimal pH around 7.5. Aft er the systemic injection of the amino analog in C57/black mice for one wee k, 1-amino-4-phenplpyridinium ion was detected in the brain. 1(N)-Amino-4-p henyl-1,2,3,6-tetrahydropyridine was proved to be cytotoxic to pheochromocy toma PC12 cells, and it may be a new neurotoxin bioactivated through the ox idation by type A and B monoamine oxidase.