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

The Journal of pharmacy and pharmacology ·Vol. 41 ·No. 7 ·1989-07-00 ·Pages 492-3

Fuller RW, Hemrick-Luecke SK

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.

MeSH Terms

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine 3,4-Dihydroxyphenylacetic Acid/metabolism Animals Corpus Striatum/drug effects,metabolism Dopamine/metabolism Homovanillic Acid/metabolism Male Mice Mice, Inbred Strains Nervous System Diseases/chemically induced,physiopathology Phenethylamines/antagonists & inhibitors Pyridines/administration & dosage,pharmacology,toxicity Receptors, Dopamine/drug effects Selegiline/antagonists & inhibitors,pharmacology

Chemicals

Phenethylamines Pyridines Receptors, Dopamine 3,4-Dihydroxyphenylacetic Acid Selegiline 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Dopamine Homovanillic Acid

Authors & Affiliations

2 authors, click to expand affiliations / ORCID

Fuller R W

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

Hemrick-Luecke S K

Article Info

Journal

The Journal of pharmacy and pharmacology

Abbr.

J Pharm Pharmacol

ISSN

0022-3573

DOI

10.1111/j.2042-7158.1989.tb06509.x

Published

1989-07-00

Pages

492-3

Language

English

Region

England

NLM ID

0376363

Subset

External Links

PubMed source DOI: 10.1111/j.2042-7158.1989.tb06509.x View journal details

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

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