Kroin J S, McCarthy R J, Penn R D, Lubenow T R, Ivankovich A D
Department of Anesthesiology, Rush Medical College, Chicago, IL 60612, USA.
Anesth Analg. 1996 Mar;82(3):627-35. doi: 10.1097/00000539-199603000-00035.
Intrathecal delivery of alpha(2)-adrenergic agonists produces an analgesic effect. However, hemodynamic side effects limit their clinical usage. To more fully characterize the effects on heart rate and arterial blood pressure of alpha(2)-adrenergic agonists, clonidine and tizanidine were injected intrathecally in conscious dogs. Both compounds produced a potent inhibition of thermal foot-withdrawal latencies at 1000 micrograms, which was blocked by the alpha(2)-adrenergic antagonist yohimbine. Tizanidine (250-500 micrograms) did not change heart rate. Clonidine (500 -2000 micrograms) and tizanidine (1000-2000 micrograms) decreased heart rate. The tizanidine effect was inhibited by yohimbine and the alpha(2)/imidazoline antagonist idazoxan, as well as the parasympathetic blocker glycopyrrolate. No drug completely inhibited the clonidine-induced bradycardia. Clonidine had a biphasic effect on arterial blood pressure, a decrease at 500 micrograms and an increase at 2000 micrograms. Tizanidine decreased arterial blood pressure at all doses. The results indicate that, while the analgesic effects of both drugs are similar, the hemodynamic responses differ. While the decrease in heart rate with tizanidine is consistent with alpha(2)-adrenergic binding and vagal action, the bradycardia induced by clonidine is more complex. In addition, the increased arterial blood pressure with high doses of clonidine, which is suggestive of a peripheral vasoconstrictive effect, does not occur with tizanidine.
鞘内注射α₂ - 肾上腺素能激动剂可产生镇痛作用。然而，血流动力学副作用限制了它们的临床应用。为了更全面地描述α₂ - 肾上腺素能激动剂对心率和动脉血压的影响，在清醒犬中鞘内注射可乐定和替扎尼定。两种化合物在1000微克时均能有效抑制热足部撤离潜伏期，该作用可被α₂ - 肾上腺素能拮抗剂育亨宾阻断。替扎尼定（250 - 500微克）不改变心率。可乐定（500 - 2000微克）和替扎尼定（1000 - 2000微克）降低心率。替扎尼定的作用被育亨宾、α₂/咪唑啉拮抗剂伊达唑胺以及副交感神经阻滞剂格隆溴铵抑制。没有药物能完全抑制可乐定引起的心动过缓。可乐定对动脉血压有双相作用，500微克时降低，2000微克时升高。替扎尼定在所有剂量下均降低动脉血压。结果表明，虽然两种药物的镇痛作用相似，但血流动力学反应不同。虽然替扎尼定引起的心率下降与α₂ - 肾上腺素能结合和迷走神经作用一致，但可乐定引起的心动过缓更为复杂。此外，高剂量可乐定引起的动脉血压升高提示外周血管收缩作用，而替扎尼定不会出现这种情况。
