Neurotoxicity of a novel local anesthetic agent, ropivacaine: The possible roles of bursts of potential and cytoplasmic second messenger
Neurotoxicity of a novel local anesthetic agent, ropivacaine: The possible roles of bursts of potential and cytoplasmic second messenger
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DOI：
10.1016/s0929-6646(08)60046-7
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发表时间：
2007-10-01
影响因子：
3.2
通讯作者：
Huang, Chi-Hsiang
中科院分区：
文献类型：
--
作者：
Lin, Pei-Lin;Fan, Shou-Zen;Huang, Chi-Hsiang
背景/目的：罗哌卡因已被证明在过量或意外静脉注射后可诱导惊厥，但其机制尚不清楚。方法：采用常规电生理技术记录罗哌卡因对非洲大蜗牛（AchatinafulicaFerussac）中枢神经元（RP 4）的作用。观察了罗哌卡因与哌唑嗪、普萘洛尔、阿托品、d-筒箭毒碱、无钙溶液、H89、U 73122、新霉素、高镁溶液和白屈菜红碱的相互作用。罗哌卡因（900 μ M）的细胞外应用可逆地引起RP 4神经元的电位爆发。在给予以下药物后，罗哌卡因引起的电位爆发未被阻断：（1）哌唑嗪，普萘洛尔，阿托品，d-筒箭毒碱;（2）无钙溶液;（3）用H89或白屈菜红碱预处理。预处理与U 73122（30 μ M）或加入新霉素（3.5 mM）或高镁溶液（30 mM）的罗哌卡因引起的电位的爆发被阻断。结论：罗哌卡因可逆地引起电位的爆发在中央蜗牛神经元。罗哌卡因引起的电位爆发与RP 4蜗牛神经元中的磷脂酶C活性相关。我们的研究结果表明，罗哌卡因诱导的神经毒性与磷脂酶C活性高度相关，磷脂酶C抑制剂可能为管理局部麻醉诱导的惊厥或其他短暂的神经毒性提供一种新的治疗方法。
Background/Purpose: Ropivacaine has been shown to induce convulsion following overdose or accidental intravenous injection, but the mechanisms are poorly understood. Using an identifiable central neuron from giant African snail, the authors studied the mechanism of ropivacaine-elicited bursts of potential and explored the possible mechanisms of ropivacaine-induced neurotoxicity.Methods: Ropivacaine action on a central neuron (RP4) of the giant African snail (Achatina fulica Ferussac) was recorded by conventional electrophysiologic technique. Interactions between ropivacaine and prazosin, propranolol, atropine, d-tubocurarine, calcium-free solution, H89, U73122, neomycin, high-magnesium solution, and chelerythrine were also observed.Results: The RP4 neuron showed spontaneous firing of action potentials. Extracellular application of ropivacaine (900 mu M) reversibly elicited bursts of potential in the RP4 neuron. The bursts of potential elicited by ropivacaine were not blocked after administration of: (1) prazosin, propranolol, atropine, d-tubocurarine; (2) calcium-free solution; and (3) pretreatment with H89 or chelerythrine. The bursts of potential elicited by ropivacaine were blocked by pretreatment with U73122 (30 mu M) or by adding neomycin (3.5 mM) or high-magnesium solution (30 mM).Conclusion: Ropivacaine reversibly elicited bursts of potential in the central snail neuron. The ropivacaine-elicited bursts of potential were associated with phospholipase C activity in the RP4 snail neuron. Our results suggest that ropivacaine-induced neurotoxicity is highly associated with phospholipase C activity and phospholipase C inhibitor may offer a novel therapeutic approach for managing local anesthetic-induced convulsion or other transient neurologic toxicity.