Pharmacology of AT1-receptor blockers

Angiotensin II mediates its haemodynamic effects by binding to specific cell-surface receptors. In humans, two receptor subtypes have been identified, designated AT(1) and AT(2). Because all major deleterious effects of angiotensin II are produced via binding to AT(1)-receptors, selective blockade of this receptor subtype should confer haemodynamic benefits, while allowing stimulation of the potentially beneficial effects mediated by AT(2)-receptors. Experimental studies using various models have consistently revealed marked differences in the receptor binding properties of different AT(1)-receptor blockers. The relative receptor binding affinities of currently available AT(1)-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-3174, 17 min for irbesartan and 5 min for losartan. Candesartan therefore binds to the AT(1)-receptor more tightly and more persistently than other AT(1)-receptor blockers. angiotensin II, candesartan, receptor pharmacology.