Pharmacological Profiles of a Novel Non-peptide Angiotensin II Type I Receptor Antagonist HR720 In Vitro and In Vivo

The pharmacological properties of 2-butyl-4-(methylthio)-1-[[2'-[[[(propylamino)carbonyl] amino]sulfonyl](1'-biphenyl)-4-yl]methyl]-1H-imidazole-5-carboxylate (HR720), a novel non-peptide angiotensin (Ang) II type I (AT1) receptor antagonist, were characterized in both in vitro and in vivo...

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Bibliographic Details
Published in:Japanese Journal of Pharmacology 1997, Vol.75 (3), p.259-266
Main Authors: Denan Jin, Keifu Song, Yuko Oka, Shinji Takai, Naotaka Shiota, Mizuo Miyazaki
Format: Article
Language:Japanese
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Summary:The pharmacological properties of 2-butyl-4-(methylthio)-1-[[2'-[[[(propylamino)carbonyl] amino]sulfonyl](1'-biphenyl)-4-yl]methyl]-1H-imidazole-5-carboxylate (HR720), a novel non-peptide angiotensin (Ang) II type I (AT1) receptor antagonist, were characterized in both in vitro and in vivo systems. In vitro autoradiography using 1251-[Sar1 , Ile8]Ang II as a ligand revealed that HR720 competitively inhibited the specific binding of the ligand to the adrenal cortex. The IC50 Value for the adrenal cortex was 1. 5 x 10-8 M, and the IC50 for medulla was 1. 4 x 10 6 M. Similar results were obtained in the adrenal cortex with CV-1 1974, a known potent ATl-receptor antagonist. Since ATI receptors are known to predominate in the adrenal cortex and AT2-receptors in the adrenal medulla, it is considered that HR720 is highly selective for AT1 receptors.
ISSN:0021-5198