Pharmacology of AT 1 -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 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 < tasosartan < losartan < eprosartan. Candesartan is also released from the receptor more slowly than other available AT 1 -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. © 2001, Informa UK Ltd All rights reserved: reproduction in whole or part not permitted. All rights reserved.