A high dose of MPTP overcomes the protective effect of selegiline against dopaminergic neurotoxicity.
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.
Fuller
R W
RW
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285.
Hemrick-Luecke
S K
SK
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009422:Nervous System Diseases / Q000139:chemically induced / Q000503:physiopathology*; D010627:Phenethylamines / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D011954:Receptors, Dopamine / Q000187:drug effects*; D012642:Selegiline / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D010627:Phenethylamines; D011725:Pyridines; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D012642:Selegiline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D006719:Homovanillic Acid