Angiotensin-converting enzyme inhibitory and antihypertensive activities of pivalopril (RHC 3659-(S)).
Pivalopril (RHC 3659-(S); (S)-N-cyclopentyl-N-(2-methyl-3-pivaloylthiopropionyl) glycine) is a new compound with a hindered sulfur group that has been compared to captopril for oral angiotensin-converting enzyme (ACE) inhibition in rats and dogs and antihypertensive activity in rats. In separate groups of conscious normotensive rats, pivalopril (0.03-1.0 mg/kg, orally [p.o.]) produced a dose-related antagonism of angiotensin I (AngI)-induced pressor effects. The ED50 for pivalopril and captopril was 0.1 mg/kg. In conscious normotensive dogs, pivalopril (incremental doses of 0.01-1.0 mg/kg, p.o.) produced a dose-related antagonism of AngI pressor effects. The ED50 was 0.17 mg/kg for pivalopril and 0.06 mg/kg for captopril. At equieffective doses the two compounds had similar durations of action. In sodium-deficient, conscious spontaneously hypertensive rats (SHR), pivalopril (1-100 mg/kg, p.o.) produced a dose-related reduction in mean arterial pressure. The potency and duration were similar to those of captopril. In the sodium-replete SHR, 5 days of oral dosing with pivalopril, 100 mg/(kg . day), decreased mean arterial pressure more effectively than captopril, 100 mg/(kg . day). No tolerance developed to the antihypertensive effect of either drug. It is concluded that pivalopril is a potent, orally effective ACE inhibitor and antihypertensive agent.
D000803:Angiotensin I / Q000037:antagonists & inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D000959:Antihypertensive Agents; D002216:Captopril / Q000494:pharmacology; D003517:Cyclopentanes / Q000494:pharmacology* / Q000627:therapeutic use; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000188:drug therapy; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000172:deficiency
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D003517:Cyclopentanes; C034144:pivalopril; D000803:Angiotensin I; D002216:Captopril; D012964:Sodium