Pharmacology of AT1-receptor blockers

Abstract

Angiotensin II mediates its haemodynamic effects by binding to specific cell-surface receptors. In humans, two receptor subtypes have been identified, designated AT1 and AT2. Because all major deleterious effects of angiotensin II are produced via binding to AT1-receptors, selective blockade of this receptor subtype should confer haemodynamic benefits, while allowing stimulation of the potentially beneficial effects mediated by AT2-receptors. Experimental studies using various models have consistently revealed marked differences in the receptor binding properties of different AT1-receptor blockers. The relative receptor binding affinities of currently available AT1-receptor blockers is candesartan > irbesartan > valsartan/EXP-3174/telmisartan > tasosartan > losartan > eprosartan. Candesartan is also released from the receptor more slowly than other available AT1-receptor blockers, with a half-life of approximately 152 min for the receptor-blocker complex, compared with 31 min for EXP-3 174, 17 min for irbesartan and 5 min for losartan. Candesartan therefore binds to the AT1-receptor more tightly and more persistently than other AT1-receptor blockers.