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Huell, Katharina; Fernandez-Duenas, Victor; Schoenberger, Matthias; Lopez-Cano, Marc; Trauner, Dirk and Ciruela, Francisco (2021): Optical Control of Adenosine-Mediated Pain Modulation. In: Bioconjugate Chemistry, Vol. 32, No. 9: pp. 1979-1983

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Adenosine receptors (ARs) play many important roles in physiology and have been recognized as potential targets for pain relief. Here, we introduce three photoswitchable adenosine derivatives that function as light-dependent agonists for ARs and confer optical control to these G protein-coupled receptors. One of our compounds, AzoAdenosine-3, was evaluated in the classical formalin model of pain. The molecule, active in the dark, was not metabolized by adenosine deaminase and effectively reduced pain perception in a light-dependent manner. These antinociceptive effects suggested a major role for A(1)R and A(3)R in peripheral-mediated pain sensitization, whereas an average adenosine-mediated antinociceptive effect will be facilitated by A(2A)R and A(2B)R. Our results demonstrate that a photoswitchable adenosine derivative can be used to map the contribution of ARs mediating analgesia in vivo.

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