Guven Mustafa, Kahraman Ibrahim, Koc Filiz, Bozdemir Hacer, Sarica Yakup, Gunay Ismail
Department of Biophysics, School of Medicine, University of Cukurova, 01330 Adana, Turkey.
Neurol Res. 2011 Jan;33(1):68-74. doi: 10.1179/016164110X12714125204191. Epub 2010 May 18.
Oxcarbazepine is an antiepileptic drug widely used for the treatment of neuropathic pain. In the present study, the effects of oxcarbazepine and lamotrigine on conduction properties in the rat sciatic nerves were examined.
The experiments were conducted with in vitro sucrose-gap technique on the isolated wistar rat sciatic nerves. The compound action potentials were obtained by tonic (single) and phasic (10, 40, and 100 Hz) stimulation.
Oxcarbazepine produced a significant concentration- and frequency-dependent reduction in the compound action potential amplitude. When the two drugs were applied at concentrations that produced equal levels of tonic (i.e., non-frequency-dependent) conduction block, oxcarbazepine produced the greatest phasic (i.e., frequency-dependent) conduction block, followed by lamotrigine. Oxcarbazepine and lamotrigine reduced the 4-aminopyridine-induced amplitude of delayed depolarization; however, oxcarbazepine had a significantly greater effect than lamotrigine.
These results suggest that oxcarbazepine produces more potent frequency-dependent conduction block than lamotrigine, and suppresses the delayed depolarization which contributes to sensory signaling and may play a role in neuropathic pain. The findings provide insight into the mechanisms of action of oxcarbazepine and lamotrigine and may help in the development of novel therapies for neuropathic pain.
奥卡西平是一种广泛用于治疗神经性疼痛的抗癫痫药物。在本研究中,检测了奥卡西平和拉莫三嗪对大鼠坐骨神经传导特性的影响。
采用体外蔗糖间隙技术对分离的Wistar大鼠坐骨神经进行实验。通过强直(单次)和相位(10、40和100Hz)刺激获得复合动作电位。
奥卡西平使复合动作电位幅度出现显著的浓度和频率依赖性降低。当以产生同等程度强直(即非频率依赖性)传导阻滞的浓度应用这两种药物时,奥卡西平产生的相位(即频率依赖性)传导阻滞最大,其次是拉莫三嗪。奥卡西平和拉莫三嗪降低了4-氨基吡啶诱导的延迟去极化幅度;然而,奥卡西平的作用明显大于拉莫三嗪。
这些结果表明,奥卡西平比拉莫三嗪产生更强效的频率依赖性传导阻滞,并抑制延迟去极化,延迟去极化有助于感觉信号传导,可能在神经性疼痛中起作用。这些发现为奥卡西平和拉莫三嗪的作用机制提供了见解,并可能有助于开发治疗神经性疼痛的新疗法。