Prevention of MPTP-induced neurotoxicity by AGN-1133 and AGN-1135, selective inhibitors of monoamine oxidase-B.

Two selective and potent inhibitors of monoamine oxidase (MAO) type B, namely AGN-1133 (N-methyl-N-propynyl-1-indanamine) and AGN-1135 (N-propynyl-1-indanamine), given to mice prior to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) protected against the neurotoxic effects of MPTP. For example, mice treated with these agents prior to MPTP, did not exhibit the decrement in the neostriatal content of dopamine and its metabolites normally seen after MPTP administration. These data lend further support to the concept that the oxidation of MPTP by MAO-B to its corresponding pyridinium analog, 1-methyl-4-phenyl-pyridinium (MPP+) is an important feature of the neurotoxic process.