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Article Dans Une Revue British Journal of Pharmacology Année : 2023

Remote local photoactivation of morphine produces analgesia without opioid‐related adverse effects

Résumé

Background and purpose: Opioid-based drugs are the gold standard medicines for pain relief. However, tolerance and several side effects (i.e., constipation, dependence) may occur upon chronic opioid administration. Photopharmacology is a promising approach to improve the benefit/risk profiles of these drugs. Thus, opioids can be locally activated with high spatiotemporal resolution, potentially minimizing systemic-mediated adverse effects. Here, we aimed at developing a morphine photo-derivative (photocaged morphine, pc-Mor), which can be activated upon light irradiation both in vitro and in vivo. Experimental approach: Light-dependent activity of pc-Mor was assessed in cell-based assays (intracellular calcium accumulation and electrophysiology) and in mice (formalin animal model of pain). In addition, tolerance, constipation, and dependence were investigated in vivo using experimental paradigms. Key results: In mice, pc-Mor was able to elicit antinociceptive effects, both using external light-irradiation (hind paw) and spinal cord implanted fibre-optics. In addition, remote morphine photoactivation was devoid of common systemic opioid-related undesired effects, namely constipation, tolerance to the analgesic effects, rewarding effects, and naloxone-induced withdrawal. Conclusion and implications: Light-dependent opioid-based drugs may allow effective analgesia without the occurrence of tolerance or the associated and severe opioid-related undesired effects.
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Dates et versions

hal-03320533 , version 1 (02-06-2022)

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Paternité - Pas d'utilisation commerciale

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Marc López‐cano, Joan Font, Ester Aso, Kristoffer Sahlholm, Gisela Cabré, et al.. Remote local photoactivation of morphine produces analgesia without opioid‐related adverse effects. British Journal of Pharmacology, 2023, 180 (7), pp.958-974. ⟨10.1111/bph.15645⟩. ⟨hal-03320533⟩
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