Medicinal chemists and pharmacologists have shed a lot of solvent in the quest to develop a painkiller that can match opioids’ effectiveness without their unwelcome side effects. Along the way, they have developed a panoply of ligands for the μ-opioid receptor. The latest new agonist comes with its own on-off switch (Cell 2026, DOI: 10.1016/j.cell.2026.09.042).
The molecule borrows a trick from rhodopsin, one of the light-sensing receptors in human eyes. Vision depends on cis-trans isomerization of rhodopsin’s ligand, retinal. When retinal absorbs a photon, it changes shape and activates rhodopsin signaling.
“This ‘logic of retinal,’ if you will, can be applied to just about any G protein–coupled receptor.”
Dirk Trauner, chemist, University of Pennsylvania