Caged-carvedilol as a new tool for visible-light photopharmacology of β-adrenoceptors in native tissues

Adrenoceptors areG protein-coupled receptors involved in a large variety of physiological processes, also under pathological conditions. This is due in large part to their ubiquitous expression in the body exerting numerous essential functions. Therefore, the possibility to control their activity with high spatial and temporal precision would constitute a valuable research tool. In this study, we present a caged version of the approved non-selective beta-adrenoceptor antagonist carvedilol, synthesized by alkylation of its secondary amine with a coumarin derivative. Introducing this photo-removable group abolished carvedilol physiological effects in cell cultures, mouse isolated perfused hearts and living zebrafish larvae. Only after visible light application, carvedilol was released and the different physiological systems were pharmacologically modulated in a similar manner as the control drug. This research provides a new photopharmacological tool for a wide range of research applications that may help in the development of future precise therapies.

Automated summary

This study presents a new photopharmacological tool that allows the control of adrenoceptor activity through light-induced release. The tool effectively modulates various physiological systems, providing potential for the development of precise therapies in the future.