The mechanism of action and the metabolism of the parkinsonian- syndrome inducing neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine) has been studied in mouse, dog, and monkey. The metabolism of radiolabelled MPTP has shown that only the pyridinum metabolite, MPP+, is accumulated in monkey brain. Distribution of that metabolite with respect to time (1, 3, or 10 days) indicated that MPP+ persists in the striatum and does not migrate toward or co-exist with the dense neuromelanin deposits in the substantia nigral cells. The conditions for the safe handling of animals treated with MPTP was evaluated; MPTP and its metabolites are not vapor borne, and treated animals can be handled safely with normal laboratory protective clothing. The neurotoxic effects of MPTP in beagle dogs has been evaluated. MPTP produces a profound and permanent loss of cells within the substantia nigra at doses similar to those effective in primates. Dogs exhibit a transient hypokinesia, but regain locomotor capability in spite of the extent of nigral cell loss. Immunoassay of MPTP and MPP+ has been improved and polyclonal rabbit antibodies characterized for their binding characteristics. Brain extracts contain substances which interfere with antigen-antibody recognition, necessitating chemical separation. A metabolism study of another parkinsonian producing neurotoxin, alpha-methyl-beta-methylaminopropionic acid (BMAA) has been initiated.
