Table 1.

Binding characteristics of different sartans to the human AT₁ angiotensin II receptor stably expressed in recombinant CHO cells

Sartan	COOH present	App. affinity versus candesartan	Dissociation t 1/2 (min)	Insurmountable (%)	Insurmountable if one step (%)
Candesartan	+	1	120	95	98.5
Olmesartan	+	0.73	75	85	97.7
EXP3174	+	0.45	30	70	94.4
Telmisartan	−	0.083	25	70	94.4
Valsartan	+	0.17	17	50	90.5
Irbesartan	−	0.15	7	30	78.9
Losartan	−	0.014	<0.1*	0	<5.4

Adapted from Van Liefde and Vauquelin, 2009; data are from Fierens et al., 1999a, 1999b; Vanderheyden et al., 2000a, 2000b; Verheijen et al., 2000; and Le et al., 2007)

A carboxyl (COOH) group at the imidazole‐derived moiety contributes to the affinity and insurmountable behaviour of the sartans (e.g. compare the characteristics of EXP3174 with those of its precursor losartan where the carboxyl group is substituted by a hydroxyl group). Dissociation half‐lives were calculated from mono‐exponential dissociation curves of tritiated sartans and from functional experiments. Their affinities relative to candesartan are from [³H]‐valsartan competition‐binding experiments. Their degree of insurmountability refers to the largest decline in maximal Ang II‐mediated response (i.e. cumulated inositol triphosphate production during 5 min, in the absence of desensitization) after 30 min preincubation with sartan alone. These experimental data are compared with the degree of insurmountability that is expected for antagonists that bind according to a one‐step reversible bimolecular process and dissociate with the cited half‐lives.

^* Taking account of a potential 5% error on the degree of insurmountability of losartan, these latter calculations suggest that it dissociates with a half‐life of less than 0.1 min.