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• W3047503656 endingPage "1923" @default.
• W3047503656 startingPage "1923" @default.
• W3047503656 abstract "As many, if not most, ligands at G protein-coupled receptor antagonists are inverse agonists, we systematically reviewed inverse agonism at the nine adrenoceptor subtypes. Except for β3-adrenoceptors, inverse agonism has been reported for each of the adrenoceptor subtypes, most often for β2-adrenoceptors, including endogenously expressed receptors in human tissues. As with other receptors, the detection and degree of inverse agonism depend on the cells and tissues under investigation, i.e., they are greatest when the model has a high intrinsic tone/constitutive activity for the response being studied. Accordingly, they may differ between parts of a tissue, for instance, atria vs. ventricles of the heart, and within a cell type, between cellular responses. The basal tone of endogenously expressed receptors is often low, leading to less consistent detection and a lesser extent of observed inverse agonism. Extent inverse agonism depends on specific molecular properties of a compound, but inverse agonism appears to be more common in certain chemical classes. While inverse agonism is a fascinating facet in attempts to mechanistically understand observed drug effects, we are skeptical whether an a priori definition of the extent of inverse agonism in the target product profile of a developmental candidate is a meaningful option in drug discovery and development." @default.
• W3047503656 created "2020-08-10" @default.
• W3047503656 creator A5047848929 @default.
• W3047503656 creator A5073004639 @default.
• W3047503656 date "2020-08-19" @default.
• W3047503656 modified "2023-09-30" @default.
• W3047503656 title "A Systematic Review of Inverse Agonism at Adrenoceptor Subtypes" @default.
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