Pharmacology of AT(1)-receptor blockers

Angiotensin II mediates its haemodynamic effects by binding to specific cel l-surface receptors. In humans, two receptor subtypes have been identified, designated AT(1) and AT(2). Because all major deleterious effects of angio tensin II are produced via binding to AT(1)-receptors, selective blockade o f this receptor subtype should confer haemodynamic benefits, while allowing stimulation of the potentially beneficial effects mediated by AT(2)-recept ors. Experimental studies using various models have consistently revealed m arked differences in the receptor binding properties of different AT(1)-rec eptor blockers. The relative receptor binding affinities of currently avail able AT(1)-receptor blockers is candesartan > irbesartan > valsartan/EXP-31 74/telmisartan > tasosartan > losartan > eprosartan. Candesartan is also re leased from the receptor more slowly than other available AT1-receptor bloc kers, with a half-life of approximately 152 min for the receptor-blocker co mplex, compared with 31 min for EXP-3174, 17 min for irbesartan and 5 min f or 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.