Binding Properties of Telmisartan (Micardis) for Human Angiotensin II Receptors.
| Accession number;03A0237822 |
| Title;Binding Properties of Telmisartan (Micardis) for Human Angiotensin II Receptors. |
| Author;SUDO KATSUMI(Yamanouchi Pharmaceutical Co., Ltd., JPN) FUNATSU TOSHIYUKI(Yamanouchi Pharmaceutical Co., Ltd., JPN) KAKUTA HIROTOSHI(Yamanouchi Pharmaceutical Co., Ltd., JPN) UEMURA TOSHIO(Yamanouchi Pharmaceutical Co., Ltd., JPN) MIYATA KEIJI(Yamanouchi Pharmaceutical Co., Ltd., JPN) |
Journal Title;Clinical Pharmacology and Therapy
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Journal Code:L1701A
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ISSN:0917-3994
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VOL.13;NO.2;PAGE.111-119(2003)
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| Figure&Table&Reference;FIG.2, TBL.2, REF.15 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;The affinities of a novel AT1 receptor antagonist telmisartan for human AT1 and AT2 receptors, and the dissociation rate constant of the compound for the AT1 receptor were investigated in comparison with those of candesartan, valsartan, losartan and an active metabolite of losartan EXP-3174. Telmisartan, candesartan, valsartan, losartan and EXP-3174 inhibited 125I-angiotensin II binding to the human AT1 receptor in a concentration-dependent manner. Ki values of these compounds were 10.9, 6.9, 41.1, 24.3 and 11.1 nM, respectively. The order of affinity for the human AT1 receptor was as follows: candesartan .GEQ. telmisartan = EXP-3174 > losartan > valsartan. On the other hand, the compounds tested up to 10,000 nM had no inhibitory effect on 125I-CGP42112A, a selective AT2 receptor radioligand, binding to the human AT2 receptor. Telmisartan, candesartan, valsartan, losartan and EXP-3174 dissociated from human AT1 receptors in a time-dependent manner. Dissociation rate constants of these compounds were 0.0028, 0.0065, 0.014, 0.012 and 0.010 min-1, respectively. Furthermore, their corresponding t1/2 values were 247, 106, 50, 57 and 70 min, respectively. The order of dissociation rate from the human AT1 receptor was as follows: valsartan .GEQ. losartan .GEQ. EXP-3174 > candesartan > telmisartan. In conclusion, the affinity and selectivity of telmisartan for the human AT1 receptor are almost equal or superior to other AT1 receptor antagonists tested. Furthermore, the dissociation rate of telmisartan from the human AT1 receptor is slower than those of the other AT1 receptor antagonists. (author abst.) |
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