title: The Alcohol Intolerance Produced by Isoniazid Is Not Due to a Disulfiram-Like Reaction Despite Aldehyde Dehydrogenase Inhibition.
abstract: OBJECTIVE
  Isoniazid (ISO) has been reported to inhibit the hepatic aldehyde dehydrogenase (ALDH) and to cause a disulfiram (DIS)-like reaction, albeit there are no reports demonstrating increased blood acetaldehyde levels after co-administration of ISO with alcohol. The aim of our study was to clarify whether the alcohol intolerance produced by ISO is indeed due to a typical DIS-like reaction.
  
  
  METHODS
  DIS and ISO were administered to Wistar rats and the hepatic ethanol (ETH) metabolizing enzyme activities along with the levels of brain monoamines were determined. Blood acetaldehyde levels were also evaluated after co-administration of ETH with DIS or ISO.
  
  
  RESULTS
  Despite inhibition of the hepatic ALDH, ISO did not result in elevated blood acetaldehyde levels after ETH administration, probably due to the induction of cytochrome P450 2E1 which theoretically leads to an increased elimination rate of acetaldehyde preventing its accumulation. Moreover, ISO produced some minor, but statistically significant, alterations in central monoaminergic neurotransmission.
  
  
  CONCLUSIONS
  Our results demonstrate for the first time that despite ALDH inhibition ISO does not provoke a typical DIS-like reaction since it does not increase blood acetaldehyde levels after co-administration with ETH. The possibility that the ETH intolerance observed in ISO treatment is a central synergistic effect cannot be excluded.
authors: Department of Pharmacology, Medical School, University of Ioannina, Ioannina, Greece.
authors: Petros N
authors: PN
authors: Karamanakos
authors: Periklis
authors: P
authors: Pappas
authors: Vasiliki
authors: V
authors: Boumba
authors: Theodoros
authors: T
authors: Vougiouklakis
authors: Marios
authors: M
authors: Marselos
mesh_terms: D000079:Acetaldehyde / Q000097:blood*; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000818:Animals; D004221:Disulfiram / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000633:toxicity*; D007538:Isoniazid / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D000431:Ethanol; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde; D004221:Disulfiram; D007538:Isoniazid