The acute convulsant effect of MPTP is dependent on intracerebral MPP+.
The administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to C57 black mice causes an acute seizure syndrome the severity of which is dose dependent; there is also a good correlation between the seizure inducing potential of MPTP and the neostriatal dopamine (DA) depletion caused by MPTP. The simultaneous administration of MPTP and MAO B inhibitors attenuates both epileptiform phenomena and neostriatal DA depletion. On the contrary diethyldithiocarbamate (DDC) exacerbates both responses. All these pharmacological manipulations are known to affect the accumulation of 1-methyl-4-phenylpyridinium ion (MPP+) the main metabolite of MPTP. Thus the present data support the hypothesis of a strict dependence of the epileptiform phenomena on the presence of MPP+. Furthermore the tight correlation existing between the severity of epileptic events and DA depletion suggests that the acute excitotoxic syndrome may contribute to the long-term toxicity of MPTP. *On leave from the Department of Neurology, University of Pisa, Pisa, Italy.
Bonuccelli
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Department of Neurological Sciences, Rush University, Rush Presbyterian St. Luke's Medical Center, Chicago, IL 60612.
Garant
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Fariello
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D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000378:metabolism / Q000494:pharmacology; D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003292:Convulsants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000737:chemistry / Q000187:drug effects / Q000503:physiopathology; D004050:Ditiocarb / Q000494:pharmacology; D004347:Drug Interactions; D004827:Epilepsy / Q000139:chemically induced* / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D006719:Homovanillic Acid / Q000032:analysis; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D020267:MPTP Poisoning; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology; D013239:Stereotyped Behavior / Q000187:drug effects
D003292:Convulsants; D008996:Monoamine Oxidase Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D006897:Hydroxyindoleacetic Acid; D004050:Ditiocarb; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D006719:Homovanillic Acid