Angiotensin converting enzyme inhibitors reduce alcohol consumption: some possible mechanisms and important conditions for its therapeutic use.
Alcoholism is a prevalent problem of contemporary society, yet there are virtually no clinically effective drugs for the management of this disorder. A previous study demonstrating the ability of angiotensin-converting enzyme (ACE) inhibitors to attenuate voluntary alcohol intake in rats prompted the suggestion that these drugs, currently marketed for the treatment of hypertension, may also be useful in dealing with human alcohol abuse. The present experiments explored in more detail the effect and possible mechanisms of action of this class of drug on alcohol consumption in rats. Experiment one demonstrated that Abutapril, a new ACE inhibitor, significantly reduced alcohol intake and that this effect could not be blocked by either an ANG II or an opiate receptor antagonist suggesting that neither the peripheral renin-angiotensin system (RAS) nor the endogenous enkephalins are involved in the ability of ACE inhibition to attenuate alcohol intake. Experiments two and three showed that ACE inhibition effectively reduced alcohol drinking faster in animals with elevated RAS activity and not at all in animals with suppressed RAS activity indicating that initial levels of RAS activity may determine the speed and ability of ACE inhibition to attenuate alcohol intake. ACE inhibitors may reduce alcohol intake by elevating a nonapeptide fragment or by elevating central ANG II levels. The assessment of this class of drugs to reduce alcohol intake in humans should include a monitoring of the initial level of activity in the renin-angiotensin system since this may be a predictor of the effectiveness of treatment with the ACE inhibitors.
Lingham
T
T
Department of Pharmacology, University of Toronto, Ontario, Canada.
Perlanski
E
E
Grupp
L A
LA
D000428:Alcohol Drinking / Q000187:drug effects*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology; D008297:Male; D009271:Naltrexone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D000804:Angiotensin II; C014805:angiotensin II, Sar(1)-Thr(8)-; D009271:Naltrexone; C052134:libenzapril