Inhibition of pyruvate dehydrogenase complex (PDHC) by antipsychotic drugs.
The effects of 11 antipsychotic drugs on the pyruvate dehydrogenase complex (PDHC) prepared from bovine heart and rat brain were investigated. All inhibited PDHC to varying extents. With clinically equivalent doses, chlorpromazine and thioridazine inhibited the most and fluphenazine and thiothixene the least. The relationship of degree of inhibition of PDHC by neuroleptics to clinical improvement of 32 outpatients treated with acetazolamide and thiamine (A + T) ancillary therapy for chronic mental illness suggests that patients treated with psychoactive drugs that inhibit PDHC the least are most likely to have a favorable response with A + T treatment.
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Nathan S. Kline Institute for Psychiatric Research, Cerebral Metabolism Laboratory, Orangeburg, NY 10962.
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D000086:Acetazolamide / Q000627:therapeutic use; D000553:Ambulatory Care; D000818:Animals; D001921:Brain / Q000201:enzymology; D002417:Cattle; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D006801:Humans; D066298:In Vitro Techniques; D001523:Mental Disorders / Q000150:complications / Q000188:drug therapy / Q000201:enzymology; D011619:Psychotropic Drugs / Q000494:pharmacology* / Q000627:therapeutic use; D011768:Pyruvate Dehydrogenase Complex / Q000037:antagonists & inhibitors*; D015325:Pyruvate Dehydrogenase Complex Deficiency Disease / Q000150:complications / Q000188:drug therapy; D051381:Rats; D013831:Thiamine / Q000627:therapeutic use
D011619:Psychotropic Drugs; D011768:Pyruvate Dehydrogenase Complex; D000086:Acetazolamide; D013831:Thiamine