Yoshitomi Tatsushi, Kohjitani Atsushi, Maeda Shigeru, Higuchi Hitoshi, Shimada Masahiko, Miyawaki Takuya
Department of Dental Anesthesiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8525, Japan.
Anesth Analg. 2008 Jul;107(1):96-101. doi: 10.1213/ane.0b013e318176be73.
Clonidine, an alpha-2 adrenoceptor agonist, is a common adjunct in both central and peripheral blocks. Dexmedetomidine, a more selective alpha-2 adrenoceptor agonist, is also known to enhance central neural blockades. Its peripheral effect, however, has not been fully elucidated. Thus, we evaluated the effect of dexmedetomidine and other alpha-2 adrenoceptor agonists on the local anesthetic action of lidocaine at the periphery and explored the mechanism involved.
alpha-2 Adrenoceptor agonists, including dexmedetomidine, clonidine, and oxymetazoline, combined with lidocaine were intracutaneously injected into the back of male guinea pigs. The test of six pinpricks was applied every 5 min until 60 min after the injection. The number of times which the prick failed to elicit a response during the 60-min period was added and the sum served as an anesthetic score indicating the degree of local anesthesia. Differences from the control value within the group were analyzed using an analysis of variance followed by a post hoc Dunnett's test. Furthermore, we evaluated the antagonism of the effect of dexmedetomidine by yohimbine, an alpha-2A, 2B, and 2C adrenoceptor antagonist, or prazosin, an alpha-1, alpha-2B, and 2C adrenoceptor antagonist, analyzed using a two-way analysis of variance.
All alpha-2 adrenoceptor agonists enhanced the degree of local anesthesia of lidocaine in a dose-dependent manner. Furthermore, yohimbine inhibited the effect of dexmedetomidine, whereas prazosin did not.
We demonstrated that alpha-2 adrenoceptor agonists enhanced the local anesthetic action of lidocaine, and suggest that dexmedetomidine acts via alpha-2A adrenoceptors.
可乐定是一种α-2肾上腺素能受体激动剂，是中枢和外周阻滞中常用的辅助药物。右美托咪定是一种更具选择性的α-2肾上腺素能受体激动剂，也已知可增强中枢神经阻滞作用。然而，其外周作用尚未完全阐明。因此，我们评估了右美托咪定和其他α-2肾上腺素能受体激动剂对利多卡因在外周的局部麻醉作用的影响，并探讨了其中涉及的机制。
将包括右美托咪定、可乐定和羟甲唑啉在内的α-2肾上腺素能受体激动剂与利多卡因联合皮内注射到雄性豚鼠背部。每隔5分钟进行一次六点针刺试验，直至注射后60分钟。将60分钟内针刺未能引起反应的次数相加，其总和作为麻醉评分，指示局部麻醉程度。使用方差分析和事后Dunnett检验分析组内与对照值的差异。此外，我们评估了α-2A、2B和2C肾上腺素能受体拮抗剂育亨宾或α-1、α-2B和2C肾上腺素能受体拮抗剂哌唑嗪对右美托咪定作用的拮抗作用，使用双向方差分析进行分析。
所有α-2肾上腺素能受体激动剂均以剂量依赖性方式增强利多卡因的局部麻醉程度。此外，育亨宾抑制右美托咪定的作用，而哌唑嗪则无此作用。
我们证明α-2肾上腺素能受体激动剂增强了利多卡因的局部麻醉作用，并表明右美托咪定通过α-2A肾上腺素能受体发挥作用。
