Kasaba Toshiharu, Onizuka Shin, Takasaki Mayumi
Department of Anesthesiology, Miyazaki Medical College, Kiyotake-Cho, Japan.
Anesth Analg. 2003 Jul;97(1):85-90, table of contents. doi: 10.1213/01.ane.0000065905.88771.0d.
The neurotoxicity of local anesthetics can be demonstrated in vitro by the collapse of growth cones and neurites in cultured neurons. We compared the neurotoxicity of procaine, mepivacaine, ropivacaine, bupivacaine, lidocaine, tetracaine, and dibucaine by using cultured neurons from the freshwater snail Lymnaea stagnalis. A solution of local anesthetics was added to the culture dish to make final concentrations ranging from 1 x 10(-6) to 2 x 10(-2) M. Morphological changes in the growth cones and neurites were observed and graded 1 (moderate) or 2 (severe). The median concentrations yielding a score of 1 were 5 x 10(-4) M for procaine, 5 x 10(-4) M for mepivacaine, 2 x 10(-4) M for ropivacaine, 2 x 10(-4) M for bupivacaine, 1 x 10(-4) M for lidocaine, 5 x 10(-5) M for tetracaine, and 2 x 10(-5) M for dibucaine. Statistically significant differences (P < 0.05) were observed between mepivacaine and ropivacaine, bupivacaine and lidocaine, lidocaine and tetracaine, and tetracaine and dibucaine. The order of neurotoxicity was procaine = mepivacaine < ropivacaine = bupivacaine < lidocaine < tetracaine < dibucaine. Although lidocaine is more toxic than bupivacaine and ropivacaine, mepivacaine, which has a similar pharmacological effect to lidocaine, has the least-adverse effects on cone growth among clinically used local anesthetics.
Systematic comparison was assessed morphologically in growth cones and neurites exposed to seven local anesthetics. The order of neurotoxicity was procaine = mepivacaine < ropivacaine = bupivacaine < lidocaine < tetracaine < dibucaine. Although lidocaine is more toxic than bupivacaine and ropivacaine, mepivacaine, which has a similar pharmacological effect to lidocaine, is the safest among clinically used local anesthetics.
局部麻醉药的神经毒性可在体外通过培养神经元中生长锥和神经突的塌陷来证明。我们使用来自淡水蜗牛椎实螺的培养神经元比较了普鲁卡因、甲哌卡因、罗哌卡因、布比卡因、利多卡因、丁卡因和地布卡因的神经毒性。将局部麻醉药溶液添加到培养皿中，使最终浓度范围为1×10⁻⁶至2×10⁻²M。观察生长锥和神经突的形态变化并分级为1（中度）或2（重度）。产生1分的中位浓度，普鲁卡因为5×10⁻⁴M，甲哌卡因为5×10⁻⁴M，罗哌卡因为2×10⁻⁴M，布比卡因为2×10⁻⁴M，利多卡因为1×10⁻⁴M，丁卡因为5×10⁻⁵M，地布卡因为2×10⁻⁵M。在甲哌卡因与罗哌卡因、布比卡因与利多卡因、利多卡因与丁卡因以及丁卡因与地布卡因之间观察到统计学上的显著差异（P<0.05）。神经毒性顺序为普鲁卡因 = 甲哌卡因 < 罗哌卡因 = 布比卡因 < 利多卡因 < 丁卡因 < 地布卡因。尽管利多卡因比布比卡因和罗哌卡因毒性更大，但与利多卡因具有相似药理作用的甲哌卡因在临床使用的局部麻醉药中对锥生长的不良影响最小。
对暴露于七种局部麻醉药的生长锥和神经突进行了形态学系统比较。神经毒性顺序为普鲁卡因 = 甲哌卡因 < 罗哌卡因 = 布比卡因 < 利多卡因 < 丁卡因 < 地布卡因。尽管利多卡因比布比卡因和罗哌卡因毒性更大，但与利多卡因具有相似药理作用的甲哌卡因是临床使用的局部麻醉药中最安全的。
