Optical control of pain in vivo with a photoactive mGlu 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 (mGlu) receptor negative allosteric modulat...

Descripción completa

Detalles Bibliográficos
Autores: Font Inglès, Joan|||0000-0001-8416-1909, López Cano, Marc|||0000-0001-8885-3726, Notartomaso, Serena|||0000-0003-4374-9233, Scarselli, Pamela|||0000-0002-4245-0849, Di Pietro, Paola|||0000-0003-1327-1961, Bresolí-Obach, Roger|||0000-0002-7819-7750, Battaglia, Giuseppe|||0000-0001-7571-3417, Malhaire, Fanny, Rovira, Xavier|||0000-0002-9764-9927, Catena, Juanlo|||0000-0002-2423-5926, Giraldo, Jesús|||0000-0001-7082-4695, Pin, Jean-Philippe|||0000-0002-1423-345X, Fernández-Dueñas, Víctor|||0000-0001-7834-2965, Goudet, Cyril|||0000-0002-8255-3535, Nonell, Santi|||0000-0002-8900-5291, Nicoletti, Ferdinando|||0000-0003-0917-443X, Llebaria, Amadeu|||0000-0002-8200-4827, Ciruela, Francisco|||0000-0003-0832-3739
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:186204
Acceso en línea:https://ddd.uab.cat/record/186204
https://dx.doi.org/urn:doi:10.7554/eLife.23545
Access Level:acceso abierto
Palabra clave:Analgesia
Optopharmacology
Pain neuraxis
Mglu5 receptor
Allosteric modulation
Mouse
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 (mGlu) 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 mGlu 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 mGlu 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.

Similares en LA Referencia