[Pharmacological profiles of candesartan cilexetil (TCV-116)]

Candesartan cilexetil has shown potent and long-lasting antihypertensive effects in clinical trials and in several hypertensive animal models. In rabbit aortic preparation, candesartan, active form of candesartan cilexetil, decreased the maximal contractile response of angiotensin II (insurmountable inhibition). This inhibitory mode was different from that of other angiotensin II receptor blockers, and showed a shift to the right in the angiotensin II-induced contraction curve. In kinetic studies using bovine adrenal cortical membrane and tritiated candesartan, both receptor association and dissociation were found to be slow. The insurmountable inhibition of candesartan in vascular contraction is the result of its tight binding and slow dissociation from AT1 receptors. These characteristics are related to the potency and long duration of action in candesartan cilexetil.