Role of alpha-2 adrenergic receptors on anesthesia and pain transmission

α2肾上腺素受体对麻醉和疼痛传递的作用

基本信息

批准号：
08457405
负责人：
DOHI Shuji
金额：
$ 4.8万
依托单位：
Gifu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457405/
关键词：
Alpha-2 adrenergic receptors Clonidine Dexmedetomidine Alpha-2 adrenoceptor Spinal Antinociception Receptor bindings Signal transduction Opioid tolerance α2-adrenergic agonists 局所麻酔薬 Extracelluallr Signal-regulated Kinase Ouabain ペ

项目摘要

For the last decade, alpha-2 adrenergic agonists such as clonidine have been extensively used for clinical anesthesia to provide better patients' care in perioperative periods. When given clonidine preoperatively as a premedicant for patients undergoing anesthesia and surgery it Would reduce requirements of inhalational and intravenous anesthetic agents, and opioids, provide stable hemodynamics, and enhance the action of vasopressors such as phenylephrine. When clonidine given intrathecally, it would produce a potent spinal antinociception and prolonged spinal anesthesia with local anesthetics. To elucidate some of mechanism(s) and roles for clinical efficacy of alpha-2 adrenoceptor agonists, we have done several studies, Using the cranial window technique, we found that clonidine produces cerebral vasoconstriction via activation of alpha-2 adrenoceptors of the pial vessels in a dose-related manner. When alpha-2 adrenoceptor agonists, clonidine, dexmedetomidine and tizanidine, were given into the epidural space or intravenously in rats, they produced almost 5 times greater antinociception with epidural administration as compared with those with their intravenous administration. The rank of order for their spinal antinociceptive action was identical with those of alpha-2 adrenergic receptor binding affinity of spinal' cord and brain. Brain alpha-2-adrenoceptors are up-regulated in morphine dependent guinea pigs and clonidine could reduced opiate withdrawal sings in morphine-dependent animals. We also found that patients given clonidine as premedicant showed a significantly augmented responses to ephedrine in propofol anesthesia to reduce epinephrine test dose for epidural anesthesia. Also we found that clonidine premedication modifies responses to alpha1- and beta-_2 adrenoceptor agonists and baroreflex sensitivity.

在过去的十年中，可乐定等α2肾上腺素受体激动剂已广泛用于临床麻醉，以在围手术期为患者提供更好的护理。当术前给予可乐定作为接受麻醉和手术的患者的术前用药时，它会减少吸入和静脉麻醉剂以及阿片类药物的需求，提供稳定的血流动力学，并增强血管加压药（如去氧肾上腺素）的作用。当可乐定鞘内给药时，它会产生有效的脊髓镇痛作用，并通过局部麻醉剂延长脊髓麻醉时间。为了阐明α-2肾上腺素受体激动剂临床疗效的一些机制和作用，我们进行了多项研究，利用颅窗技术，我们发现可乐定通过激活软脑膜血管的α-2肾上腺素受体而产生脑血管收缩以剂量相关的方式。当将 α-2 肾上腺素受体激动剂（可乐定、右美托咪定和替扎尼定）注入大鼠硬膜外腔或静脉注射时，硬膜外给药产生的镇痛作用比静脉内给药强近 5 倍。它们的脊髓镇痛作用的顺序与脊髓和脑的α2肾上腺素受体结合亲和力的顺序相同。吗啡依赖性豚鼠的大脑α-2-肾上腺素受体上调，可乐定可以减少吗啡依赖性动物的阿片戒断症状。我们还发现，术前给予可乐定的患者在异丙酚麻醉中对麻黄碱的反应显着增强，以减少硬膜外麻醉的肾上腺素测试剂量。我们还发现可乐定术前用药可以改变对 α1- 和 β-2 肾上腺素受体激动剂的反应以及压力反射敏感性。