Illuminating Phenylazopyridines to Photoswitch Metabotropic Glutamate Receptors: From the Flask to the Animals

Xavier Gómez-Santacana, Silvia Pittolo, Xavier Rovira, Marc Lopez, Charleine Zussy, James A.R. Dalton, Adèle Faucherre, Chris Jopling, Jean Philippe Pin, Francisco Ciruela, Cyril Goudet, Jesús Giraldo, Pau Gorostiza, Amadeu Llebaria

Research output: Contribution to journalArticleResearchpeer-review

31 Citations (Scopus)


© 2016 American Chemical Society. Phenylazopyridines are photoisomerizable compounds with high potential to control biological functions with light. We have obtained a series of phenylazopyridines with light dependent activity as negative allosteric modulators (NAM) of metabotropic glutamate receptor subtype 5 (mGlu5). Here we describe the factors needed to achieve an operational molecular photoisomerization and its effective translation into in vitro and in vivo receptor photoswitching, which includes zebrafish larva motility and the regulation of the antinociceptive effects in mice. The combination of light and some specific phenylazopyridine ligands displays atypical pharmacological profiles, including light-dependent receptor overactivation, which can be observed both in vitro and in vivo. Remarkably, the localized administration of light and a photoswitchable compound in the peripheral tissues of rodents or in the brain amygdalae results in an illumination-dependent analgesic effect. The results reveal a robust translation of the phenylazopyridine photoisomerization to a precise photoregulation of biological activity.
Original languageEnglish
Pages (from-to)81-91
JournalACS Central Science
Issue number1
Publication statusPublished - 25 Jan 2017


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