Pharmacological Characterization of KR-31125, a Novel Nonpeptide AT1 Receptor Antagonist

Abstract

KR-31125 (2-butyl-5-dimethoxymethyl-6-phenyl-7-methyl-3-[[2'-(1H-tetrazol-5-yl)] CGP 42112A to human recombinant AT2 receptor. The binding action was also confirmed as a competitive mode that was identical to the previously studied compound, losartan. In addition, KR-31125 caused a nonparallel shift to the right in the concentration response curves to angiotensin II with a 30-80% decrease in the maximum contractile responses (pKB: 7.63). Compared to the previous studies with losartan that showed a parallel right shift in the maximum contractile responses to AII (pA2: 7.59), KR-31125 presented a different mode of action with a similar potency to losartan. These results demonstrate that KR-31125 is a highly potent and AT1 selective angiotensin II receptor antagonist that can be applied to the fields of new diagnostic and research tools with upcoming in vivo study results.