Title:
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Optical control of pain in vivo with a photoactive mGlu5 receptor negative allosteric modulator
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Author:
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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
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Other authors:
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Universitat Ramon Llull. IQS |
Abstract:
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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. |
Publication date:
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2017-04 |
Subject (UDC):
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615 - Farmacologia. Terapèutica. Toxicologia. Radiologia |
Subject(s):
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Dolor--Tractament Analgèsia Malalties cròniques Light-operated drugs Complex diseases Optical control |
Rights:
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L'accés als continguts d'aquest document queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons:http://creativecommons.org/licenses/by/4.0/
© L'autor/a |
Pages:
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20 p. |
Document type:
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Article Article - Published version |
DOI:
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https://doi.org/10.7554/elife.23545
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Published by:
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eLife Sciences Publications
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Publish at:
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eLIFE. Vol.6 (2017), e23545
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