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Haloperidol shows striking structural similarities to the neurotoxin 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetra\u2010hydropyridine, which produces parkinsonism apparently through inhibition of NADH:ubiquinone oxidoreductase (complex I) of the mitochondrial electron transport chain. We now report that haloperidol chlorpromazine, and thiothixine inhibit complex I in vitro in rat brain mitochondria. Clozapine, an atypical antipsychotic reported to have little or no extrapyramidal toxicity, also inhibits complex I, but at a significantly higher concentration. Neuroleptic treated patients have significant depression of platelet complex I activity similar to that seen in idiopathic Parkinson's disease. Complex I inhibition may be associated with the extrapyramidal side effects of these drugs.<\/jats:p>","DOI":"10.1002\/ana.410330516","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T15:09:39Z","timestamp":1104592179000},"page":"512-517","source":"Crossref","is-referenced-by-count":179,"title":["Neuroleptic medications inhibit complex I of the electron transport chain"],"prefix":"10.1002","volume":"33","author":[{"given":"Carolyn","family":"Burkhardt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young\u2010Hwa","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Filley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"W. 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