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Journal of Pharmacology and Experimental Therapeutics

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Abstract

Antihypertensive effects of CI-907 (indolapril): a novel nonsulfhydryl angiotensin converting enzyme inhibitor.

M J Ryan, D M Boucher, D M Cohen, A D Essenburg, T C Major, T E Mertz, B J Olszewski, A E Randolph, R M Singer and H R Kaplan
Journal of Pharmacology and Experimental Therapeutics February 1984, 228 (2) 312-318;
M J Ryan
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D M Boucher
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D M Cohen
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A D Essenburg
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T C Major
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T E Mertz
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B J Olszewski
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A E Randolph
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R M Singer
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H R Kaplan
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Abstract

CI-907 is a new orally active nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor. Monoester (prodrug) and diacid forms produced concentration related ACE inhibition in guinea-pig serum (IC50 for monoester, 1.7 X 10(-7) M and for diacid, 2.6 X 10(-9) M). In isolated rabbit aortic rings and in rat and dog autonomic studies, CI-907 is highly specific in suppressing the contractile or pressor responses to angiotensin I. In two-kidney, one-clip Goldblatt hypertensive rats, single daily doses (0.03-30 mg/kg p.o.) produced dose-dependent decreases in blood pressure; 3 mg/kg lowered blood pressure to normotensive levels. In the spontaneously hypertensive rat, subacute administration of CI-907 (30 mg/kg/day for 5 days) produced the same decrease in blood pressure as that obtained in the renal hypertensive rat. In diuretic-pretreated renal hypertensive dogs, 10 mg/kg normalized blood pressure. For equivalent drops in blood pressure, heart rate increases were less in CI-907 than in enalapril-treated renal hypertensive dogs. No side effects were observed with CI-907 in any of the conscious animals. The antihypertensive response to CI-907 (0.03-1.0 mg/kg p.o.) was found to correlate with inhibition of vascular tissue ACE, but not plasma or brain ACE in two-kidney, one-clip renal hypertensive rats. These studies indicate that CI-907 is a potent antihypertensive agent with a heart rate profile different from enalapril.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 228, Issue 2
1 Feb 1984
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Abstract

Antihypertensive effects of CI-907 (indolapril): a novel nonsulfhydryl angiotensin converting enzyme inhibitor.

M J Ryan, D M Boucher, D M Cohen, A D Essenburg, T C Major, T E Mertz, B J Olszewski, A E Randolph, R M Singer and H R Kaplan
Journal of Pharmacology and Experimental Therapeutics February 1, 1984, 228 (2) 312-318;

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Abstract

Antihypertensive effects of CI-907 (indolapril): a novel nonsulfhydryl angiotensin converting enzyme inhibitor.

M J Ryan, D M Boucher, D M Cohen, A D Essenburg, T C Major, T E Mertz, B J Olszewski, A E Randolph, R M Singer and H R Kaplan
Journal of Pharmacology and Experimental Therapeutics February 1, 1984, 228 (2) 312-318;
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