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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Detalles Bibliográficos
Autores: Nonell, Santi, Bresolí Obach, Roger, Font Inglès, Joan, López-Cano, Marc, Notartomaso, Serena, Scarselli, Pamela, Di Pietro, Paola, Battaglia, Giuseppe, Malhaire, Fanny, Rovira, Xavier, Catena, Juanlo, Giraldo, Jesús, Pin, Jean-Philippe, Fernández-Dueñas, Víctor, Goudet, Cyril, Nicoletti, Ferdinando, Llebaria, Amadeu, Ciruela, Francisco
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:20.500.14342/993
Acceso en línea:http://hdl.handle.net/20.500.14342/993
https://doi.org/10.7554/elife.23545
Access Level:acceso abierto
Palabra clave:Dolor--Tractament
Analgèsia
Malalties cròniques
Light-operated drugs
Complex diseases
Optical control
615
Descripción
Sumario: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.

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