Effect of bestatin, an aminopeptidase inhibitor, on alcohol intake in alcohol-preferring P rats.
Bestatin is an aminopeptidase and enkephalinase inhibitor that elevates the levels of angiotensin II and angiotensin III. Although it has been used for years in the treatment of various forms of cancer, its application as an antialcohol drug has not been explored, despite its ability to stimulate angiotensin activity. The present study assesses the ability of bestatin to reduce chronic alcohol consumption in the genetically selected high alcohol-consuming P rats. Two groups of P rats were given 24-hr access to food, water, and 10% (v/v) alcohol. After a baseline period, half the rats received the saline vehicle and the other half ascending doses of bestatin (2.5, 10, 20, and 30 mg/kg, bid). Each dose was administered for a minimum of 7 days. Bestatin had little effect on water intake or weight gain, but did produce a dose-dependent reduction in alcohol intake that averaged 33% and was sustained over the course of the 1-month period of administration. Years of experience with bestatin have shown it to be safe and free of major side effects. The present findings suggest that bestatin (Ubenimex) might also be useful in the treatment of alcohol abuse in humans.
Szczepanska
R
R
Department of Pharmacology, University of Toronto, Ontario, Canada.
Harding
S
S
Grupp
L A
LA
D000427:Alcohol Deterrents / Q000494:pharmacology*; D000437:Alcoholism / Q000201:enzymology / Q000235:genetics / Q000534:rehabilitation*; D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000427:Alcohol Deterrents; D011480:Protease Inhibitors; D000626:Aminopeptidases; D007930:Leucine; C012211:ubenimex