title: 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: Department of Cardiovascular Pharmacology, Merck Research Laboratories, West Point, PA 19486, USA.
authors: S D
authors: SD
authors: Kivlighn
authors: G J
authors: GJ
authors: Zingaro
authors: R A
authors: RA
authors: Gabel
authors: T P
authors: TP
authors: Broten
authors: R S
authors: RS
authors: Chang
authors: D L
authors: DL
authors: Ondeyka
authors: N B
authors: NB
authors: Mantlo
authors: R E
authors: RE
authors: Gibson
authors: W J
authors: WJ
authors: Greenlee
authors: P K
authors: PK
authors: Siegl
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D007093:Imidazoles / Q000378:metabolism / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D011725:Pyridines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D007093:Imidazoles; C098860:L 163017; D011725:Pyridines; D011945:Receptors, Angiotensin; D000804:Angiotensin II