Persistent depletion of striatal dopamine and its metabolites in mice by TMMP, an analogue of MPTP

Abstract

TMMP (1-methyl-4-[methylpyrrol-2-yl]-1,2,3,6-tetrahydropyridine) mimicked MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in causing persistent depletion of striatal dopamine and its metabolites one week after the last of four daily subcutaneous injections in mice. MMPP (1-methyl-4-[1-methylpyrrol-2-yl]-4-piperidinol) produced no depletion of dopamine or its metabolites under these conditions. None of the three compounds affected dopamine or its metabolites when administered orally. TMMP was even more rapidly oxidized by type B monoamine oxidase in-vitro than was MPTP, but MMPP was a very poor substrate for the enzyme. The lack of neurotoxicity of MMPP toward nigrostriatal dopamine neurons when it was given orally or subcutaneously to mice contrasts with previously reported results in monkeys, in which case MMPP was reported to be neurotoxic.