In vivo pharmacology of L-159,913, a new highly potent and selective nonpeptide angiotensin II receptor antagonist
| Autor: | Flanagan Kl, Robert A. Gabel, Linda W. Schaffer, Salah D. Kivlighn, William J. Greenlee, Linda L. Chang, Wallace T. Ashton, Terry W. Schorn, Peter K. S. Siegl, Gloria J. Zingaro |
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| Rok vydání: | 1995 |
| Předmět: |
Male
medicine.medical_specialty Enalaprilat Pan troglodytes Physiology medicine.drug_class Natriuresis Tetrazoles Angiotensin II receptor antagonist Blood Pressure Pharmacology Kidney Losartan Rats Sprague-Dawley chemistry.chemical_compound Angiotensin Receptor Antagonists Dogs Internal medicine Renin–angiotensin system Renin Internal Medicine medicine Animals Aldosterone Antihypertensive Agents Receptors Angiotensin Angiotensin II Biphenyl Compounds Antagonist Imidazoles General Medicine Triazoles Receptor antagonist Macaca mulatta Rats Endocrinology chemistry Hypertension Potassium Female medicine.drug |
| Zdroj: | Clinical and experimental hypertension (New York, N.Y. : 1993). 17(6) |
| ISSN: | 1064-1963 |
| Popis: | The present study was designed to characterize the in vivo pharmacology of L-159,913 (4-[[2'-(N-benzoylsulfamoyl)biphenyl-4-yl]-5butyl-2,4-dihydr o-2- [2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-one); a potent All receptor antagonist. In normotensive rats, dogs, rhesus monkeys, and chimpanzees, L-159,913 inhibited All-induced elevations in blood pressure. In conscious rats, the relative potencies (ED50) were 0.51 mg/kg i.v. and 0.72 mg/kg p.o. Duration of action with single i.v. or p.o. doses exceeded 6 hr in rats. L-159,913 was 3 times less potent than losartan in rats and equipotent to losartan in monkeys. All induced elevation of plasma aldosterone in rats was also inhibited by L-159,913. L-159,913 was antihypertensive in high renin hypertensive rats (aortic coarctation). The maximum hypotensive response to an acute dose of L-159,913 (10 mg/kg, po) was equal to that of enalaprilat (0.3 mg/kg, iv) in this renin dependent animal model. In conscious normotensive dogs, L-159,913 had a moderate diuretic, natriuretic and kaliuretic response with no effect on glomerular filtration rate, effective renal plasma flow or filtration fraction, suggesting a tubular site of action. L-159,913 is a selective and potent All receptor antagonist with good oral activity, long duration of action and antihypertensive efficacy. |
| Databáze: | OpenAIRE |
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