DEXMEDETOMIDINE PRODUCES A HYPNOTIC ANESTHETIC ACTION IN RATS VIA ACTIVATION OF CENTRAL ALPHA-2 ADRENOCEPTORS
DEXMEDETOMIDINE PRODUCES A HYPNOTIC ANESTHETIC ACTION IN RATS VIA ACTIVATION OF CENTRAL ALPHA-2 ADRENOCEPTORS
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DOI：
10.1097/00000542-198907000-00014
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发表时间：
1989-07-01
期刊：
影响因子：
8.8
通讯作者：
MAZE, M
中科院分区：
文献类型：
--
作者：
DOZE, VA;CHEN, BX;MAZE, M
右美托咪定是一种高选择性和强效α-2肾上腺素受体激动剂，可使大鼠氟烷麻醉剂需求量降低90%以上。本研究检测了右美托咪定是否在大鼠中产生催眠麻醉作用。右美托咪定在大鼠中诱导了以翻正反射丧失为特征的高度麻醉状态。0.1 mg/kg.在0.1 - 3 mg/kg剂量范围内，该反应呈剂量依赖性。穿过血脑屏障的α-2肾上腺素受体拮抗剂（阿替美唑和咪唑克生）以剂量依赖性方式降低了右美托咪定的催眠麻醉作用。相比之下，α-2拮抗剂L-659，066不渗透到CNS中，不影响右美托咪定诱导的催眠。其他肾上腺素受体拮抗剂不仅不能降低右美托咪定的麻醉作用，在某些情况下甚至增强了这种作用。因此，α-1肾上腺素受体拮抗剂哌唑嗪显著增强了右美托咪定的催眠麻醉特性。具有β-2受体阻断特性的拮抗剂也增强了右美托咪定诱导的催眠。选择性β-1受体拮抗剂不影响右美托咪定的催眠作用。这些结果表明，右美托咪定通过激活中枢α-2-肾上腺素受体在大鼠中产生催眠麻醉作用。
Dexmedetomidine, a highly selective and potent alpha-2 adrenoceptor agonist, reduces halothane anesthetic requirements by over 90% in rats. The present study exmined whether dexmedetomidine produces a hypnotic-anesthetic action in rats. Dexmedetomidine induced a hypnotic-anesthetic state in rats characterized by loss of righting reflex at doses .gtoreq. 0.1 mg/kg. This response was dose-dependent between 0.1 and 3 mg/kg. Alpha-2 adrenoceptor antagonists that cross the blood-brain barrier (atipamezole and idazoxan) decreased the hypnotic-anesthetic action of dexmedetomidine in a dose-dependent fashion. In contrast, the alpha-2 antagonist, L-659,066, which does not penetrate into the CNS did not affect dexmedetomidine-induced hypnosis. Antagonists for the other adrenoceptors not only failed to reduce the hypnotic-anesthetic action of dexmedetomidine but in some cases even potentiated this effect. Thus, prazosin, an alpha-1 adrenoceptor antagonist, significantly enhanced the hypnotic-anesthetic property of dexmedetomidine. Antagonists with beta-2 receptor blocking properties also enhanced dexmedetomidine-induced hypnosis. Selective beta-1 receptor antagonists did not affect the hypnotic action of dexmedetomidine. These results suggest that dexmedetomidine produces a hypnotic-anesthetic action in rats via activation of central alpha-2-adrenoceptors.