Optical control of pain in vivo with a photoactive mGlu5 receptor negative 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 of the metabotropic glutamate type 5 (mGlu5) receptor negative allosteric modula...

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Bibliographic Details
Authors: Font, Joan, López-Cano, Marc, Notartomaso, Serena, Scarselli, Pamela, Di Pietro, Paola Di, Bresolí-Obach, Roger, Battaglia, Giuseppe, Malhaire, Fanny, Rovira, Xavier, Catena, Juan Lorenzo, Giraldo, Jesús, Pin, Jean Philippe, Fernández-Dueñas, Víctor, Goudet, Cyril, Nonell, Santi, Nicoletti, Ferdinando, Llebaria, Amadeu, Ciruela, Francisco
Format: article
Status:Published version
Publication Date:2017
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/151772
Online Access:http://hdl.handle.net/10261/151772
Access Level:Open access
Keyword:mGlu5
receptor negative allosteric modulator
Description
Summary: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 of the metabotropic glutamate type 5 (mGlu5) receptor negative allosteric modulator raseglurant. Violet light illumination of JF-NP-26 induces a photochemical reaction prompting the active-drug’s release, which effectively controls mGlu5 receptor activity both in ectopic expressing systems and in striatal primary neurons. Systemic administration in mice followed by local light-emitting diode (LED)-based illumination, either of the thalamus or the peripheral tissues, induced JF-NP-26-mediated light-dependent analgesia both in neuropathic and in acute/tonic inflammatory pain models. These data offer the first example of optical control of analgesia in vivo using a photocaged mGlu5 receptor negative allosteric modulator. This approach shows potential for precisely targeting, in time and space, endogenous receptors, which may allow a better management of difficult-to-treat disorders. © Font et al.

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