Zavala-Tecuapetla Cecilia, Manjarrez-Marmolejo Joaquín, Ramírez-Jarquín Josué Orlando, Rivera-Cerecedo Claudia Verónica
Laboratory of Physiology of Reticular Formation, National Institute of Neurology and Neurosurgery, Insurgentes Sur 3877, La Fama, Mexico City 14269, Mexico.
Department of Molecular Neuropathology, Institute of Cellular Physiology, National Autonomous University of Mexico, Circuito Exterior s/n, Ciudad Universitaria, Mexico City 04510, Mexico.
Brain Sci. 2022 May 11;12(5):629. doi: 10.3390/brainsci12050629.
Approximately 30% of epileptic patients develop Drug-Resistant Epilepsy. Based on evidence that shows a loss of efficacy in some sodium channel blocker antiseizure drugs in epilepsy, we focus our study on assessing the anticonvulsant efficacy of different sodium channel blockers on carbamazepine (CBZ)-resistant seizures generated using the window-pentylenetetrazole (PTZ) kindling model to verify whether one of these drugs presents some anticonvulsant effect that could have potential therapeutic use. Wistar rats were treated with a subthreshold dose of PTZ (35 mg/kg) three times/week. Fully kindled rats were then treated with a single dose of CBZ (40 mg/kg i.p.) at 2, 9 and 16 days after their last kindling stimulation to obtain CBZ-resistant rats. Right after, sodium channel blockers were tested for anticonvulsant action (lamotrigine, 30 mg/kg i.p.; eslicarbazepine, 150 or 300 mg/kg i.p.; ranolazine, 10, 20 or 40 mg/kg i.p.). Behavioral parameters included severity, latency or duration of convulsions. Our data showed for the first time directly that eslicarbazepine does have an anticonvulsant effect over CBZ-resistant seizures, while lamotrigine shows drug resistance and ranolazine demonstrates severe seizure worsening. It is of potential therapeutic relevance that eslicarbazepine could be useful to control seizures resistant to common sodium channel blockers such as CBZ.
大约30%的癫痫患者会发展为药物难治性癫痫。基于一些证据表明某些钠通道阻滞剂抗癫痫药物在癫痫治疗中疗效丧失，我们将研究重点放在评估不同钠通道阻滞剂对使用戊四氮（PTZ）点燃模型产生的卡马西平（CBZ）耐药性癫痫发作的抗惊厥疗效上，以验证这些药物中的一种是否具有可能具有潜在治疗用途的抗惊厥作用。Wistar大鼠每周接受三次阈下剂量的PTZ（35mg/kg）治疗。在最后一次点燃刺激后的第2、9和16天，对完全点燃的大鼠单次注射CBZ（40mg/kg腹腔注射）以获得CBZ耐药大鼠。之后，测试钠通道阻滞剂的抗惊厥作用（拉莫三嗪，30mg/kg腹腔注射；艾司利卡西平，150或300mg/kg腹腔注射；雷诺嗪，10、20或40mg/kg腹腔注射）。行为参数包括惊厥的严重程度、潜伏期或持续时间。我们的数据首次直接表明，艾司利卡西平对CBZ耐药性癫痫发作确实具有抗惊厥作用，而拉莫三嗪表现出耐药性，雷诺嗪则表现出严重的癫痫发作恶化。艾司利卡西平可能有助于控制对常见钠通道阻滞剂如CBZ耐药的癫痫发作，这具有潜在的治疗意义。
