Cerebral and peripheral neurotoxicity of chlorpromazine and ethanol interaction: implications for alcohol and aldehyde dehydrogenase.
The effects of certain experimental variables on rodents brain and liver alcohol--(ADH) and aldehyde-dehydrogenase (LALDH) were evaluated. The in vivo and in vitro effect of chlorpromazine on these enzymes was determined. Short-term housing under complete darkness differentially inhibited ADH and ALDH in distinct brain regions with ADH showing more sensitivity than ALDH. The hepatic enzymes studied were not affected by such housing conditions but a non-competitive inhibition of L-ALDH occurred as a consequence of exposure to UV lighting for 3 consecutive weeks. Short-term treatment with chlorpromazine inhibited striatal ADH which was not affected by experimentally-induced hypothermia. Likewise, both hepatic and testicular ADH were noncompetitively inhibited in vitro by chlorpromazine. The results suggest sensitivity of brain and hepatic ADH to environmental housing conditions and indicate a similarity between peripheral and cerebral ADH responses to chlorpromazine. The modulation of ADH and/or ALDH may facilitate the formation of endogenous biogenic amines derived alkaloids which have been implicated in alcohol and extrapyramidal side effects.
Messiha
F S
FS
Texas Tech University Health Sciences Center, School of Medicine, Lubbock.
D000426:Alcohol Dehydrogenase / Q000187:drug effects; D000444:Aldehyde Dehydrogenase / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002746:Chlorpromazine / Q000633:toxicity*; D004347:Drug Interactions; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D007035:Hypothermia / Q000201:enzymology; D066298:In Vitro Techniques; D008027:Light; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010525:Peripheral Nerves / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics
D000431:Ethanol; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; D002746:Chlorpromazine