Comparative toxicity of MPTP, MPP+ and 3,3-dimethyl-MPDP+ to dopaminergic neurons of the rat substantia nigra.

The depletion of dopamine and its metabolites in the striatum of rats was assessed 3 weeks after the unilateral intranigral infusion of different doses of MPTP, its ultimate metabolite MPP+, and 3,3-DM-MPDP+, a non-oxidizable analog of the initial MPTP metabolite 2,3-MPDP+. MPP+ was found to be 2-3 orders of magnitude more toxic than the other two agents, consistent with the view that it is primarily responsible for MPTP neurotoxicity.