Sawaki K, Ouchi K, Sato T, Kawaguchi M
Department of Pharmacology, Tokyo Dental College, Chiba, Japan.
Jpn J Pharmacol. 1991 Jul;56(3):327-35. doi: 10.1254/jjp.56.327.
The effects of local anesthetics (procaine and lidocaine) on the gamma-aminobutyric acid (GABA) and L-glutamic acid (Glu) levels in rat spinal cord were studied during the convulsive process. The present study also investigated the influence of central GABA manipulations on the local anesthetic-induced convulsions. An increase in spinal GABA levels was observed at the preconvulsive and convulsive states after administration of procaine (170 mg/kg, i.p.) or lidocaine (120 mg/kg, i.p.), which induced clonic convulsions; in the depressive state, GABA levels returned to normal; in all states, Glu levels were unchanged. Semicarbazide (25-100 mg/kg, i.p.), a glutamic acid decarboxylase inhibitor, produced a decrease in spinal GABA content and strongly enhanced both local anesthetic-induced convulsions as shown by a shortening of the latency and an increase in the mortality. Aminooxyacetic acid (AOAA; 10-40 mg-kg, i.p.), a GABA transaminase inhibitor, dose-dependently increased spinal GABA content and markedly suppressed procaine-induced convulsions. However, lidocaine-induced convulsions were enhanced by AOAA. These results suggest that the spinal GABA neuron may respond to the convulsions induced by local anesthetics. Furthermore, there is a clear relationship between spinal GABA content and procaine-induced, but not lidocaine-induced, convulsions.
在惊厥过程中，研究了局部麻醉药（普鲁卡因和利多卡因）对大鼠脊髓中γ-氨基丁酸（GABA）和L-谷氨酸（Glu）水平的影响。本研究还调查了中枢GABA调控对局部麻醉药诱导惊厥的影响。腹腔注射普鲁卡因（170mg/kg）或利多卡因（120mg/kg）诱导阵挛性惊厥后，在惊厥前期和惊厥期观察到脊髓GABA水平升高；在抑制期，GABA水平恢复正常；在所有状态下，Glu水平均未改变。氨基脲（25 - 100mg/kg，腹腔注射），一种谷氨酸脱羧酶抑制剂，可使脊髓GABA含量降低，并显著增强局部麻醉药诱导的惊厥，表现为潜伏期缩短和死亡率增加。氨基氧乙酸（AOAA；10 - 40mg/kg，腹腔注射），一种GABA转氨酶抑制剂，剂量依赖性地增加脊髓GABA含量，并显著抑制普鲁卡因诱导的惊厥。然而，AOAA增强了利多卡因诱导的惊厥。这些结果表明，脊髓GABA神经元可能对局部麻醉药诱导的惊厥有反应。此外，脊髓GABA含量与普鲁卡因诱导的惊厥之间存在明显关系，但与利多卡因诱导的惊厥无关。
