Binding Affinity of Candesartan, Losartan, Telmisartan and Valsartan with Angiotensin II Receptor 1 Subtype

Abstract

This study was designed to examine the interaction in the binding of selective angiotensin II receptor antagonists towards angiotensin II type 1 receptor. The AT₁ antagonists used in this study were valsartan, candesartan and losartan. Wild type AT₁ receptors were transiently expressed in COS-7 cells and the expressed protein was isolated. The binding affinities of agonist and these four AT₁ antagonists were determined towards AT₁ receptors with the help of radioligand binding studies. The binding affinity of candesartan has been found to be maximum having a pKi value of 8.61±0.21 whereas losartan showed lowest binding affinity among the antagonists (pKi=7.17±0.07). Telmisartan also showed high (pKi=8.19±0.04) and valsartan had moderate binding affinity (pKi=7.65±0.12) towards AT₁ receptors. The results of the study suggested that candesartan interacts very strongly with the receptor which is consistent with the maximum number of binding sites of in the chemical structure of candesartan. On the other hand, losartan has lower number of binding sites with the amino acid residues of AT₁ receptor and as a result it showed the minimum affinity towards the receptor.

DOI: http://dx.doi.org/10.3329/bpj.v16i1.14484

Bangladesh Pharmaceutical Journal 16(1): 10-14, 2013