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 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.
Unger
T
T
Institute of Pharmacology, Christian-AIbrechts-University, Kiel, Germany. th.unger@pharmakologie.uni-kiel.de
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D011485:Protein Binding / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000378:metabolism
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000804:Angiotensin II