Weinger M B, Bednarczyk J M
Department of Anesthesiology, University of California, San Diego.
Pharmacol Biochem Behav. 1994 Nov;49(3):523-9. doi: 10.1016/0091-3057(94)90064-7.
Atipamezole is a new, highly selective alpha2-adrenoceptor antagonist currently undergoing clinical trials as an antagonist for dexmedetomidine, a potent alpha2 agonist with sedative and analgesic properties. It has previously been demonstrated that dexmedetomidine, acting at central alpha2 adrenoceptors, antagonizes opiate-induced muscle rigidity. However, the role of endogenous alpha2-adrenergic systems in opiate-induced rigidity remains to be elucidated. The present study was designed to assess the effects of atipamezole on basal muscle tone and on alfentanil-induced muscle rigidity in the rat. Muscle tone was measured using gastrocnemius electromyography (EMG). After a 15-min baseline, saline or atipamezole (0.3 or 1.0 mg/kg) was administered, and 10 min later, saline or alfentanil (50, 150, or 300 micrograms/kg) was injected subcutaneously. Data were collected for an additional 60 min. Atipamezole (1.0 mg/kg) pretreatment (in the absence of alfentanil) produced a small increase in tonic EMG activity when compared with saline pretreatment. After saline pretreatment, significant muscle rigidity occurred in the two highest alfentanil dose groups. Atipamezole (0.3 and 1.0 mg/kg) augmented alfentanil-induced muscle rigidity. The ability of the alpha2 antagonist to potentiate both basal muscle tone and alfentanil-induced rigidity suggests that endogenous adrenergic activity and/or direct alpha2-adrenoceptor interaction with opioid receptors mediate opiate-induced muscle rigidity. These findings may be of clinical as well as basic neuropharmacological interest.
阿替美唑是一种新型、高选择性α2 -肾上腺素能受体拮抗剂，目前正在进行临床试验，作为右美托咪定的拮抗剂。右美托咪定是一种强效α2激动剂，具有镇静和镇痛特性。此前已有研究表明，右美托咪定作用于中枢α2肾上腺素能受体，可拮抗阿片类药物诱导的肌肉强直。然而，内源性α2 -肾上腺素能系统在阿片类药物诱导的强直中的作用仍有待阐明。本研究旨在评估阿替美唑对大鼠基础肌张力以及对阿芬太尼诱导的肌肉强直的影响。使用腓肠肌肌电图（EMG）测量肌张力。在15分钟的基线期后，给予生理盐水或阿替美唑（0.3或1.0毫克/千克），10分钟后，皮下注射生理盐水或阿芬太尼（50、150或300微克/千克）。再收集60分钟的数据。与生理盐水预处理相比，阿替美唑（1.0毫克/千克）预处理（在无阿芬太尼的情况下）使强直EMG活动略有增加。生理盐水预处理后，两个最高阿芬太尼剂量组出现明显的肌肉强直。阿替美唑（0.3和1.0毫克/千克）增强了阿芬太尼诱导的肌肉强直。α2拮抗剂增强基础肌张力和阿芬太尼诱导的强直的能力表明，内源性肾上腺素能活性和/或α2 -肾上腺素能受体与阿片受体的直接相互作用介导了阿片类药物诱导的肌肉强直。这些发现可能在临床以及基础神经药理学方面都具有重要意义。
