This study assessed the ability of α and α-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 agonist phenylephrine, (5) α antagonist prazosin, (6) α antagonist BMY-7378, (7) α agonist clonidine, (8) α antagonist yohimbine or (9) vehicle. All µ-opioid antagonists dose-dependently reversed fentanyl-induced locomotor and ventilatory depression. While the α 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.

中文翻译：

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靶向α1-和α2-肾上腺素能受体作为芬太尼引起的运动和通气抑制的对策


本研究评估了 α 和 α-肾上腺素能药物减少芬太尼引起的运动和通气抑制的能力。给予大鼠盐水或芬太尼，然后：（1）纳曲酮，（2）纳洛酮，（3）纳美芬，（4）α激动剂去氧肾上腺素，（5）α拮抗剂哌唑嗪，（6）α拮抗剂BMY-7378，（7 ) α 激动剂可乐定，(8) α 拮抗剂育亨宾或(9) 媒介物。所有μ-阿片拮抗剂均可剂量依赖性地逆转芬太尼引起的运动和通气抑制。虽然α药物不会改变芬太尼的作用，但无论是否使用芬太尼，可乐定都会剂量依赖性地降低运动和呼吸。相反，单独给予低剂量（0.3-1 mg/kg）育亨宾可刺激通气，而较高剂量（>1 mg/kg）可部分逆转（~50%）芬太尼引起的通气抑制，但不能逆转运动抑制。高剂量的育亨宾与次优剂量的纳曲酮组合可逆转芬太尼引起的通气抑制，这表明存在相加性。育亨宾可能与纳曲酮联合作为有效的辅助对策剂来挽救芬太尼引起的通气抑制。