Premium
The in vitro pharmacological profile of KR31080, a nonpeptide AT 1 receptor antagonist
Author(s) -
Hong KW,
Kim CD,
Lee SH,
Yoo SE
Publication year - 1998
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1998.tb00925.x
Subject(s) - losartan , receptor , angiotensin ii , antagonism , competitive antagonist , antagonist , medicine , angiotensin receptor , endocrinology , receptor antagonist , chemistry , pharmacology , biology , biochemistry
Summary— KR31080 (2‐butyl‐5‐methyl‐6‐(1‐oxopyridin‐2‐yl)‐3‐[[2′‐(1H‐tetrazol‐5‐yl) biphenyl‐4‐yl]methyl]‐3H‐imidazo[4,5‐b] pyridine) is a potent inhibitor of angiotensin type 1 (AT 1 ) receptors in rabbit aorta and human recombinant AT 1 receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration‐response curves to angiotensin II (All) with decreased maximal response (pD' 2 = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [ 125 I]AII binding to rabbit aortic membranes (AT, receptors) and [ 125 I][Sar 1 , Ile 8 ]AII binding to human recombinant AT 1 receptors in a concentration‐dependent manner with IC 50 values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [ 125 I)AII binding to bovine cerebellum membranes (ÀT 2 receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT 1 receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT 1 selective angiotensin receptor antagonist which exerts a competitive antagonism in the [ 125 I]AII binding assay and insurmountable AT 1 receptor antagonism in the functional study.