Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its toxic metabolites on the physicochemical property of the liposomal membrane in relation to their cytochrome P-450 inhibition

Abstract

The effects of the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and its toxic metabolites MPDP+ (1-methyl-4-phenyl-2,3-dihydropryridinium) and MPP+ (1-methyl-4-phenylpyridinium) on liposomal membrane were assessed using fluorescence-polarization and carboxyfluorescein leakage studies as well as in biological membrane preparations. Of the three compounds, MPTP was found to cause the greatest perturbation of membrane followed by MPDP+ and then MPP+. The ability of the three toxins to inhibit cytochrome P-450 enzyme activity (a microsomal membrane-bound enzyme system) was also studied and their relative potency was again found to be MPTP > MPDP+ > MPP+. The changes in the physicochemical property of the liposomal membrane can be related to the ability of the neurotoxins's ability to inhibit cytochrome P-450 activity.