Bestatin, an aminopeptidase B inhibitor, selectively reduces alcohol intake in rats.
Extensive research has shown that manipulations that augment activity in the renin-angiotensin system can reduce alcohol intake. Inhibition of aminopeptidase B and M can prolong the action of angiotensin (ANG) II and ANG III by preventing their degradation. This study assessed the ability of bestatin, an aminopeptidase B and M inhibitor, to decrease alcohol intake. Bestatin produced a dose-dependent reduction in alcohol intake without altering water intake. The angiotensin antagonist Sar1Thr3-ANG II, however, did not attenuate the effect of bestatin, suggesting that the reduction in alcohol intake was mediated by a system other than the renin-angiotensin system. Bestatin (Ubenimex) is used extensively in Japan as an anticancer agent. It has a low toxicity and is readily absorbed after oral administration. Although further research is needed to uncover the mechanism of its effect, the potential of this drug as an adjunct for the treatment of alcohol abuse should be evaluated.
Szczepanska
R
R
Primary Mechanisms Department, Addiction Research Foundation of Ontario, Toronto, Canada.
Grupp
L A
LA
D000428:Alcohol Drinking / Q000503:physiopathology*; D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000903:Antibiotics, Antineoplastic; D000626:Aminopeptidases; C019721:aminopeptidase B; D007930:Leucine; C012211:ubenimex