Comparison of morphine, oxycodone and the biased MOR agonist SR-17018 for tolerance and efficacy in mouse models of pain.

Autor: Pantouli F; Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, Jupiter, FL, USA., Grim TW; Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, Jupiter, FL, USA., Schmid CL; Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, Jupiter, FL, USA., Acevedo-Canabal A; Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, Jupiter, FL, USA., Kennedy NM; Departments of Molecular Medicine and Chemistry, The Scripps Research Institute, Jupiter, FL, USA., Cameron MD; Departments of Molecular Medicine and Chemistry, The Scripps Research Institute, Jupiter, FL, USA., Bannister TD; Departments of Molecular Medicine and Chemistry, The Scripps Research Institute, Jupiter, FL, USA., Bohn LM; Departments of Molecular Medicine and Neuroscience, The Scripps Research Institute, Jupiter, FL, USA. Electronic address: LBohn@scripps.edu.
Jazyk: angličtina
Zdroj: Neuropharmacology [Neuropharmacology] 2021 Mar 01; Vol. 185, pp. 108439. Date of Electronic Publication: 2020 Dec 17.
DOI: 10.1016/j.neuropharm.2020.108439
Abstrakt: The mu opioid receptor-selective agonist, SR-17018, preferentially activates GTPγS binding over βarrestin2 recruitment in cellular assays, thereby demonstrating signaling bias. In mice, SR-17018 stimulates GTPγS binding in brainstem and produces antinociception with potencies similar to morphine. However, it produces much less respiratory suppression and mice do not develop antinociceptive tolerance in the hot plate assay upon repeated dosing. Herein we evaluate the effects of acute and repeated dosing of SR-17018, oxycodone and morphine in additional models of pain-related behaviors. In the mouse warm water tail immersion assay, an assessment of spinal reflex to thermal nociception, repeated administration of SR-17018 produces tolerance as does morphine and oxycodone. SR-17018 retains efficacy in a formalin-induced inflammatory pain model upon repeated dosing, while oxycodone does not. In a chemotherapeutic-induced neuropathy pain model SR-17018 is more potent and efficacious than morphine or oxycodone, moreover, this efficacy is retained upon repeated dosing of SR-17018. These findings demonstrate that, with the exception of the tail flick test, SR-17018 retains efficacy upon chronic treatment across several pain models.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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