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2021-08-06

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cc-by-nc (c) López-Cano, Marc et al., 2021
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/230165

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

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Recurs relacionat

https://doi.org/10.1111/bph.15645

Resum

Background and purpose: Opioid-based drugs are the gold standard medicines for pain relief. However, tolerance and several side effects (i.e. constipation and 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), which can be activated upon light irradiation both in vitro and in vivo. Experimental approach: Light-dependent activity of pc-morphine 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-morphine 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.

Matèries

Efectes secundaris dels medicaments, Morfina, Fotofarmacologia

Matèries (anglès)

Drug side effects, Morphine, Photopharmacology

Citació

Col·leccions

Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

LÓPEZ-CANO, Marc, et al. Remote local photoactivation of morphine produces analgesia without opioid-related adverse effects. British Journal of Pharmacology. 2021. Vol. 180, num. 7, pags. 958-974. ISSN 0007-1188. [consulted: 28 of August of 2026]. Available at: https://hdl.handle.net/2445/230165

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