An electrochemical study of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and its oxidation products

Abstract Cyclic voltammetric and chronoamperometric experiments were performed on the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and its oxidative metabolites, 1-methyl-4-phenyl-2,3-dihydropyridinium ion (MPDP + ) and 1-methyl-4-phenylpyridinium ion (MPP + ). In neutral phosphate buffer electrolyte, MPTP underwent a 2-electron, 1-proton electrooxidation to MPDP + according to an ECE mechanism where U 2 o U 1 o . Further oxidation could be achieved in alkaline solution. MPDP + could be reduced to the radical state ( U o ⩽ −0.560 V versus SHE) followed by dimerization and other side reactions. It was also shown that MPDP + gradually disproportionates to produce MPTP and MPP + . With an U o = −1.067±0.010 V, MPP + underwent a 1-electron reduction, followed by dimerization. The redox potentials of MPP + and possibly even MPDP + were beyond the limits of known physiological reducing potentials; therefore, the primary cytotoxic action of MPP + does not proceed via redox cycling of its reduction radical, as do other pyridinium-based toxins such as methyl viologen.