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How can the differences among AT1-receptor antagonists Be explained?

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Abstract

Over the last few years we have seen a new class of antihypertensive drug evolve, the angiotensin II subtype 1 receptor antagonists. Hypothetically, all substances in this class should have the same effect on blood pressure and on end-organ damage as they all block the AT1 receptor. However, there are distinctions between them that may explain the significant and clinically important differences that seem to exist within this class of drug. An explanation for the differences may be found in receptor-antagonist kinetics. The receptor-antagonist interaction may be fitted to a two-state, two-step model which determines how large a part of the binding that will be surmountable and how large a part that will be insurmountable. The proportion of surmountable/insurmountable binding fits nicely to the duration of binding of the antagonist to the receptor, which may be translated into efficacy for the antagonist as outlined in the following review.

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  1. AstraZeneca R&D Mölndal, Integrative Pharmacology, S-431 83, Mölndal, Sweden

    Peter Morsing

  2. Department of Molecular and Biochemical Pharmacology, Institute for Molecular Biology and Biotechnology, Free University of Brussels (VUB), Paardenstraat 65, B-1640, Sint-Genesius Rode, Belgium

    Georges Vauquelin

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Morsing, P., Vauquelin, G. How can the differences among AT1-receptor antagonists Be explained?. Cell Biochem Biophys 35, 89–102 (2001). https://doi.org/10.1385/CBB:35:1:89

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