Inhibition of dopamine uptake by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a cause of parkinsonism.

N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine has been reported to cause parkinsonism in man and monkeys, producing behavioral effects within 5 min of administration. The compound reversibly and competively inhibited (IC50 = 2 microM) dopamine uptake into PC12, a clonal line of rat pheochromocytoma cells that store and secrete dopamine and acetylcholine. Uptake of choline and 2-deoxyglucose was not affected. Prolonged exposure to the compound was lethal to PC12; survivors of this treatment lost the ability to store dopamine and acetylcholine and to extend neurites upon incubation with nerve growth factor.