General pharmacology of the novel angiotensin converting enzyme inhibitor alacepril. 1st communication: Effects on cardiovascular, visceral and renal functions and on blood.
The effects of 1-[(S)-3-acetylthio-2-methylpropanoyl]-L-prolyl-L-phenylalanine (alacepril, DU-1219) an antihypertensive compound with angiotensin converting enzyme inhibitory activity, and its metabolite, desacetyl-alacepril (DU-1227), on the cardiovascular and autonomic nervous systems and on the blood were compared with those of captopril in the experimental animals. Alacepril and DU-1227 at the i.v. dose of 10 mg/kg gradually lowered the diastolic blood pressure in pentobarbital anesthetized dogs. Captopril showed similar effects. However, the former two compounds showed triphasic effects on the carotid blood flow, i.e., transient increase immediately after the injection, second increase 2 min later, and gradual decrease 20-30 min later. The second increase by DU-1227 was more potent than that by alacepril. Alacepril, DU-1227 and captopril did not affect the pressor responses induced by norepinephrine in anesthetized cats. The contractions of the nictitating membrane in cats induced by electrical stimulation of the cervical sympathetic nerve or epinephrine were depressed with high doses of these three compounds. Captopril potentiated the contractions induced by bradykinin in isolated guinea-pig ileum, while alacepril and DU-1227 were without effect. These three compounds neither affected the resting tension of isolated ileum in guinea-pigs and rabbits nor the contractions induced by acetylcholine, histamine, serotonin and nicotine of isolated guinea-pig ileum. Alacepril at the oral dose of 60 mg/kg decreased the total acidity in pylorus ligated rats, and at higher doses depressed the intestinal charcoal meal passage in mice. Alacepril at comparatively low doses decreased the urine volume with slight reduction of Na+ and K+ excretions in saline-loaded rats.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001341:Autonomic Nervous System / Q000187:drug effects*; D001777:Blood Coagulation / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology; D002415:Cats; D004064:Digestive System / Q000187:drug effects; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects*; D008297:Male; D051379:Mice; D009130:Muscle, Smooth / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009541:Nictitating Membrane / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D051381:Rats
D000959:Antihypertensive Agents; C048162:desacetyl-alacepril; D002216:Captopril