Glycine receptors (GlyRs) are essential for maintaining excitatory/inhibitory balance in neuronal circuits that control reflexes and rhythmic motor behaviors. We have developed Glyght, a GlyR ligand controlled with light. It is selective over other Cys-loop receptors, is active in vivo, and displays an allosteric mechanism of action. The photomanipulation of glycinergic neurotransmission opens new avenues to understanding inhibitory circuits in intact animals and to developing drug-based phototherapies. Last but not least, Glyght constitutes a novel molecular scaffold for glycine receptor pharmacology, and offers the opportunity to expand its limited molecular toolbox.
Reference
Gomila, Alexandre M. J.; Rustler, Karin; Maleeva, Galyna; Nin-Hil, Alba; Wutz, Daniel; Bautista-Barrufet, Antoni; Rovira, Xavier; Bosch, Miquel; Mukhametova, Elvira; Petukhova, Elena; Ponomareva, Dania; Mukhamedyarov, Marat; Peiretti, Franck; Alfonso-Prieto, Mercedes; Rovira, Carme; Koenig, Burkhard; Bregestovski, Piotr; Gorostiza, Pau 2020, ‘Photocontrol of Endogenous Glycine Receptors In Vivo’, Cell Chemical Biology, 27, 11, 1425 – +.
A photoswitchable derivative of a benzodiazepine (Glyght) has been found to selectively inhibit glycine receptors in a light-dependent manner, both in vitro and in intact wildtype animals.