Optical control of pain in vivo with a photoactive mGlu5 receptor negative allosteric modulator

• DOI: 10.7554/elife.23545
• Publication Date: 2017-04-11T00:01:37Z
• Authors: Joan Font; Marc López-Cano; Serena Notartomaso; Pamela Scarselli; Paola Di Pietro; Roger Bresolí-Obach; Giuseppe Battaglia; Fanny Malhaire; Xavier Rovira; Juanlo Catena; Jesús Giraldo; Jean-Philippe Pin; Víctor Fernández-...; Cyril Goudet; Santi Nonell; Ferdinando Nicoletti; Amadeu Llebaria; Francisco Ciruela
• Keywords: Allosteric modulator

Light-operated drugs constitute a major target in drug discovery, since they may provide spatiotemporal resolution for the treatment of complex diseases (i.e. chronic pain). JF-NP-26 is an inactive photocaged derivative metabotropic glutamate type 5 (mGlu5) receptor negative allosteric modulator raseglurant. Violet light illumination induces photochemical reaction prompting active-drug’s release, which effectively controls mGlu5 activity both ectopic expressing systems and striatal primary neurons. Systemic administration mice followed by local light-emitting diode (LED)-based illumination, either thalamus or peripheral tissues, induced JF-NP-26-mediated light-dependent analgesia neuropathic acute/tonic inflammatory pain models. These data offer first example optical control vivo using modulator. This approach shows potential precisely targeting, time space, endogenous receptors, allow better management difficult-to-treat disorders.