Targeting α 1 - and α 2 -adrenergic receptors as a countermeasure for fentanyl-induced locomotor and ventilatory depression.

Autor: Shaykin JD; Department of Psychology, University of Kentucky, Lexington, KY, USA., Denehy ED; Department of Psychology, University of Kentucky, Lexington, KY, USA., Martin JR; Department of Psychology, University of Kentucky, Lexington, KY, USA., Chandler CM; Department of Psychology, University of Kentucky, Lexington, KY, USA., Luo D; College of Pharmacy, University of Kentucky, Lexington, KY, USA., Taylor CE; Spinal Cord and Brain Injury Research Center (SCoBIRC) and Department of Neuroscience, University of Kentucky, Lexington, KY, USA., Sunshine MD; Spinal Cord and Brain Injury Research Center (SCoBIRC) and Department of Neuroscience, University of Kentucky, Lexington, KY, USA., Turner JR; College of Pharmacy, University of Kentucky, Lexington, KY, USA., Alilain WJ; Spinal Cord and Brain Injury Research Center (SCoBIRC) and Department of Neuroscience, University of Kentucky, Lexington, KY, USA., Prisinzano TE; College of Pharmacy, University of Kentucky, Lexington, KY, USA., Bardo MT; Department of Psychology, University of Kentucky, Lexington, KY, USA. Electronic address: mbardo@uky.edu.
Jazyk: angličtina
Zdroj: Environmental toxicology and pharmacology [Environ Toxicol Pharmacol] 2024 Sep; Vol. 110, pp. 104527. Date of Electronic Publication: 2024 Aug 04.
DOI: 10.1016/j.etap.2024.104527
Abstrakt: This study assessed the ability of α 1 and α 2 -adrenergic drugs to decrease fentanyl-induced locomotor and ventilatory depression. Rats were given saline or fentanyl, followed by: (1) naltrexone, (2) naloxone, (3) nalmefene, (4) α 1 agonist phenylephrine, (5) α 1 antagonist prazosin, (6) α 1D antagonist BMY-7378, (7) α 2 agonist clonidine, (8) α 2 antagonist yohimbine or (9) vehicle. All µ-opioid antagonists dose-dependently reversed fentanyl-induced locomotor and ventilatory depression. While the α 1 drugs did not alter the effects of fentanyl, clonidine dose-dependently decreased locomotion and respiration with and without fentanyl. Conversely, yohimbine given at a low dose (0.3-1 mg/kg) stimulated ventilation when given alone and higher doses (>1 mg/kg) partially reversed (∼50 %) fentanyl-induced ventilatory depression, but not locomotor depression. High doses of yohimbine in combination with a suboptimal dose of naltrexone reversed fentanyl-induced ventilatory depression, suggestive of additivity. Yohimbine may serve as an effective adjunctive countermeasure agent combined with naltrexone to rescue fentanyl-induced ventilatory depression.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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