In vivo pharmacology of an angiotensin AT1 receptor antagonist with balanced affinity for AT2 receptors.

Abstract

L-163,017 (6-[benzoylamino]-7-methyl-2-propyl-3-[[2'-(N-(3-methyl-1-butoxy) carbonylaminosulfonyl)[1,1']-biphenyl-4-yl]methyl]-3H-imidazo[4,5- b]pyridine) is a potent, orally active, nonpeptide angiotensin II receptor antagonist. Conscious rats and dogs were dosed p.o. and i.v.; in both species the plasma bioequivalents are similar at the angiotensin AT1 and AT2 receptor sites indicating balanced activity is maintained in vivo. L-163,017 prevents the pressor response to intravenous (i.v.) angiotensin II in the conscious rat, dog, and rhesus monkey. L-163,017 also significantly reduces blood pressure in a renin-dependent model of hypertension, similar to an angiotensin converting enzyme inhibitor (Enalapril) and an angiotensin AT1 receptor-selective antagonist (L-159,282). These studies indicate that neither the angiotensin AT2 receptor nor bradykinin is important in the acute antihypertensive activity of angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists.

• Authors: S D Kivlighn, G J Zingaro, R A Gabel, T P Broten, R S Chang, D L Ondeyka, N B Mantlo, R E Gibson, W J Greenlee, P K Siegl
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 294 Issue 2-3 Pg. 439-50 (Dec 29 1995) ISSN: 0014-2999 [Print] Netherlands
• PMID: 8750704 (Publication Type: Journal Article)

Chemical References

• Angiotensin Receptor Antagonists
• Antihypertensive Agents
• Imidazoles
• L 163017
• Pyridines
• Receptors, Angiotensin
• Angiotensin II

Topics

• Angiotensin II (antagonists & inhibitors)
• Angiotensin Receptor Antagonists
• Animals
• Antihypertensive Agents (pharmacology)
• Biological Availability
• Blood Pressure (drug effects)
• Dogs
• Female
• Imidazoles (metabolism, pharmacology)
• Macaca mulatta
• Male
• Pyridines (metabolism, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Angiotensin (metabolism)