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

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 U₂^o < U₁^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.