Neuroleptic medications inhibit complex I of the electron transport chain
Carolyn Burkhardt MD
Department of Neurology, University of Colorado School of Medicine, Denver, CO
Search for more papers by this authorJames P. Kelly MD
Department of Neurology, University of Colorado School of Medicine, Denver, CO
Neurosurgery, University of Colorado School of Medicine, Denver, CO
Psychiatry, University of Colorado School of Medicine, Denver, CO
Search for more papers by this authorYoung-Hwa Lim
Department of Neurology, University of Colorado School of Medicine, Denver, CO
Search for more papers by this authorChristopher M. Filley MD
Department of Neurology, University of Colorado School of Medicine, Denver, CO
Psychiatry, University of Colorado School of Medicine, Denver, CO
Search for more papers by this authorCorresponding Author
Dr. W. Davis Parker Jr MD
Department of Neurology, University of Colorado School of Medicine, Denver, CO
Pediatrics, University of Colorado School of Medicine, Denver, CO
Box C233, University of Colorado Health Sciences Center, 4200 E. 9th Avenue, Denver, CO 80262Search for more papers by this authorCarolyn Burkhardt MD
Department of Neurology, University of Colorado School of Medicine, Denver, CO
Search for more papers by this authorJames P. Kelly MD
Department of Neurology, University of Colorado School of Medicine, Denver, CO
Neurosurgery, University of Colorado School of Medicine, Denver, CO
Psychiatry, University of Colorado School of Medicine, Denver, CO
Search for more papers by this authorYoung-Hwa Lim
Department of Neurology, University of Colorado School of Medicine, Denver, CO
Search for more papers by this authorChristopher M. Filley MD
Department of Neurology, University of Colorado School of Medicine, Denver, CO
Psychiatry, University of Colorado School of Medicine, Denver, CO
Search for more papers by this authorCorresponding Author
Dr. W. Davis Parker Jr MD
Department of Neurology, University of Colorado School of Medicine, Denver, CO
Pediatrics, University of Colorado School of Medicine, Denver, CO
Box C233, University of Colorado Health Sciences Center, 4200 E. 9th Avenue, Denver, CO 80262Search for more papers by this authorAbstract
Neuroleptic medications are prescribed to millions of patients, but their use is limited by potentially irreversible extrapyramidal side effects. Haloperidol shows striking structural similarities to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine, 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.
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