Suppression of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity in mouse brain by piroheptine and trihexyphenidyl.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces a parkinsonian state in monkeys and humans and a marked 3,4-dihydroxyphenylethylamine (dopamine) depletion in mouse striatum. In this study, we found that pretreatment with 3-(10,11,-dihydro-5H-dibenzo-[a,d]-cycloheptan-5-ylidene)-1-ethyl- 2- methylpyrrolidine (piroheptine), an anticholinergic drug which also inhibits dopamine uptake completely prevented loss of striatal dopamine in MPTP-treated mice. Trihexyphenidyl partially protected against the neurotoxicity of MPTP. However, clomipramine, a selective 5-hydroxytryptamine uptake inhibitor, did not prevent the loss of striatal dopamine. Piroheptine is another agent which was found to prevent MPTP neurotoxicity.
Saitoh
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Department of Neurology, Jichi Medical School, Tochigi, Japan.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002997:Clomipramine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004347:Drug Interactions; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010276:Parasympatholytics / Q000494:pharmacology*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D011725:Pyridines / Q000037:antagonists & inhibitors*; D011759:Pyrrolidines / Q000494:pharmacology*; D014282:Trihexyphenidyl / Q000494:pharmacology*
D003986:Dibenzocycloheptenes; D010276:Parasympatholytics; D011725:Pyridines; D011759:Pyrrolidines; D015102:3,4-Dihydroxyphenylacetic Acid; D014282:Trihexyphenidyl; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C055566:piroheptine; D002997:Clomipramine; D004298:Dopamine