Captopril and hydrochlorothiazide (Capozide) combine to enhance the reduction in voluntary alcohol intake in rats.
The effect of Capozide, the combination of captopril with a hydrochlorothiazide diuretic, on voluntary alcohol intake was assessed in two experiments. In experiment 1 naive rats who were maintained on ad libitum food and water were given daily 40-min access to a 6% (w/v) alcohol solution and water. Daily intraperitoneal injections of captopril (10 mg/kg) reduced alcohol intake, but the combination of captopril (5 and 10 mg/kg) and hydrochlorothiazide (2.5, 5, and 10 mg/kg) enhanced the reduction in intake. In experiment 2, captopril alone, hydrochlorothiazide alone, and the combination of captopril and hydrochlorothiazide were again administered daily in the limited access procedure. Captopril (10 mg/kg) again reduced alcohol intake as did all three doses of hydrochlorothiazide (2.5, 5, and 10 mg/kg). Compared with the individual effects of captopril and hydrochlorothiazide, Capozide exerted a supra-additive reduction in alcohol intake. These effects were not due to drug-induced changes in the pharmacokinetics of alcohol. Taken together these results demonstrate an enhanced potency of Capozide in suppressing alcohol intake and invite their testing in a population of hypertensive alcoholics and alcohol abusers.
Robertson
J M
JM
Primary Mechanisms Department, Addiction Research Foundation of Ontario, Toronto, Canada.
Harding
S
S
Grupp
L A
LA
D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects / Q000502:physiology; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D000431:Ethanol / Q000493:pharmacokinetics; D006852:Hydrochlorothiazide / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
D004338:Drug Combinations; C044959:captopril, hydrochlorothiazide drug combination; D006852:Hydrochlorothiazide; D000431:Ethanol; D002216:Captopril