Adrenergic Modulation With Photochromic Ligands
Davia Prischich, Alexandre M. J. Gomila, Santiago Milla‐Navarro, Gemma Sangüesa, Rebeca Dı́ez-Alarcia, Beatrice Preda, Carlo Matera, Montserrat Batlle, Laura Ramírez, Ernest Giralt, Jordi Hernando, Eduard Guasch, J. Javier Meana, Pedro de la Villa, Pau Gorostiza
Abstract
Adrenoceptors are ubiquitous and mediate important autonomic functions as well as modulating arousal, cognition, and pain on a central level. Understanding these physiological processes and their underlying neural circuits requires manipulating adrenergic neurotransmission with high spatio-temporal precision. Here we present a first generation of photochromic ligands (adrenoswitches) obtained via azologization of a class of cyclic amidines related to the known ligand clonidine. Their pharmacology, photochromism, bioavailability, and lack of toxicity allow for broad biological applications, as demonstrated by controlling locomotion in zebrafish and pupillary responses in mice.