A high dose of MPTP overcomes the protective effect of selegiline against dopaminergic neurotoxicity

Author:

Fuller Ray W1,Hemrick-Luecke Susan K1

Affiliation:

1. Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA

Abstract

Abstract 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) at 90 mg kg−1 s.c., a dose lethal in non-pretreated mice, was well tolerated in selegiline ((—)-deprenyl)-pretreated mice and produced persistent depletion of striatal dopamine and its metabolites one week after the last of four daily injections. The protective effect of selegiline against dopaminergic neurotoxicity of MPTP can thus be overridden by a high dose of MPTP that would be lethal without selegiline pretreatment.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

Reference14 articles.

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3. Lowering of epinephrine concentration in rat brain by 2, 3-dichloro-α-methylbenzylamine, an inhibitor of norepinephrine N-methyltransferase;Fuller;Biochem. Pharmacol.,1977

4. Deprenyl protection against striatal dopamine depletion by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine in mice;Fuller;Res. Commun. Subst. Abuse,1984

5. Comparison of the effects of two 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine analogs, 1-methyl-4-(2-thienyl)-1, 2, 3, 6-tetrahydropyridine and 1-methyl-4-(3-thienyl)-1, 2, 3, 6-tetrahydropyridine, on monoamine oxidase in vitro and on dopamine in mouse brain;Fuller;J. Pharmacol. Exp. Ther.,1987

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