Dynamic mechanisms of non-classical antagonism by competitive AT1 receptor antagonists

Michael J. Lew, James Ziogas, Arthur Christopoulos

Research output: Contribution to journalReview ArticleResearchpeer-review

43 Citations (Scopus)

Abstract

Selective competitive angiotensin AT1 receptor antagonists exhibit diverse patterns of antagonism of angiotensin-II-mediated responses in functional assays. These range from the classical parallel rightward shift of agonist concentration-response curves with no depression of the maximum response to an apparently straightforward insurmountable antagonism with complete depression of the maximum response and no rightward shift. This article reviews some earlier equilibrium-based models that have been used to explain the insurmountable antagonism, and suggests that a kinetic model might provide a more satisfactory account of the observations. Such a model might provide deeper insights into the pharmacology of G-protein-coupled receptors than the more popular equilibrium models. Copyright (C) 2000 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)376-381
Number of pages6
JournalTrends in Pharmacological Sciences
Volume21
Issue number10
DOIs
Publication statusPublished - 1 Oct 2000
Externally publishedYes

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