A Parkinson-like neurologic deficit in primates is caused by a novel 4-substituted piperidine

A neurologic deficit characterized by hypokinesia, postural flexion, and to a lesser extent, rigidity, tremor and myoclonus, has been observed in cynomolgus monkeys following administration of 1-methyl-4-(1-methylpyrrol-2-yl)-4-piperidinol (MMPP), a novel 4-substituted piperidine. The syndrome, similar to that described for 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), developed within 3-7 days after oral or i.v. dosing, and was accompanied by lesions in the substantia nigra. The behavioral syndrome was seen to a lesser extent in dogs but not in rats. MMPP contains a hydroxyl group on the 4-position of the pyridine ring; the corresponding dehydration product was inactive.