title: Tryptophan in alcoholism treatment II: inhibition of the rat liver mitochondrial low Km aldehyde dehydrogenase activity, elevation of blood acetaldehyde concentration and induction of aversion to alcohol by combined administration of tryptophan and benserazide.
abstract: OBJECTIVE
  The aims were to provide proofs of mechanism and principle by establishing the ability of the amino acid L-tryptophan (Trp) combined with the kynureninase inhibitor benserazide (BSZ) to inhibit the liver mitochondrial low K(m) aldehyde dehydrogenase (ALDH) activity after administration and in vivo and to induce aversion to alcohol.
  
  
  METHODS
  Trp, BSZ or both were administered to male Wistar rats and ALDH activity was determined both in vitro in liver homogenates and in vivo (by measuring acetaldehyde accumulation in blood after ethanol administration). Alcohol consumption was studied in an aversion model in rats and in alcohol-preferring C57 mice.
  
  
  RESULTS
  Combined administration of Trp + BSZ, but neither compound alone, produced a strong inhibition of ALDH activity and an increase in blood acetaldehyde concentration after ethanol, and induced aversion to alcohol in rats and decreased preference in mice. Another kynureninase inhibitor, carbidopa, induced aversion to alcohol by itself, which was reversed by Trp co-administration.
  
  
  CONCLUSIONS
  The present results establish a prior art for the use of a combination of Trp plus BSZ in the treatment of alcoholism by aversion, which merits rapid clinical development.
authors: The Cardiff School of Health Sciences, University of Wales Institute Cardiff, Western Avenue, Cardiff, Wales, UK. abadawy@uwic.ac.uk
authors: Abdulla A-B
authors: AA
authors: Badawy
authors: Samina
authors: S
authors: Bano
authors: Alex
authors: A
authors: Steptoe
mesh_terms: D000079:Acetaldehyde / Q000097:blood; D000427:Alcohol Deterrents / Q000008:administration & dosage / Q000494:pharmacology*; D000428:Alcohol Drinking / Q000517:prevention & control*; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001545:Benserazide / Q000008:administration & dosage / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D006867:Hydrolases / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D055502:Secondary Prevention; D014364:Tryptophan / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000427:Alcohol Deterrents; D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D000431:Ethanol; D001545:Benserazide; D014364:Tryptophan; D000444:Aldehyde Dehydrogenase; D006867:Hydrolases; C021480:kynureninase; D000079:Acetaldehyde