Adrenergic Modulation With Photochromic Ligands

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. Adrenoswitches, a class of novel azoheteroaryl photoswitches, were developed to achieve on‐demand modulation of adrenergic neurotransmission by means of illumination at specific wavelengths. Their versatility to photocontrol biological systems is demonstrated in vivo employing two different animal models, zebrafish and mice.