Laboratory of Neuropharmacology, Department of Physiological Sciences, Institute of Biological Sciences, University of Brasília, Brasília 70910-900, Brazil.
Toxins (Basel). 2024 Aug 5;16(8):342. doi: 10.3390/toxins16080342.
Epilepsy, a neurological disorder characterized by excessive neuronal activity and synchronized electrical discharges, ranks among the most prevalent global neurological conditions. Despite common use, antiepileptic drugs often result in adverse effects and lack effectiveness in controlling seizures in temporal lobe epilepsy (TLE) patients. Recent research explored the potential of occidentalin-1202, a peptide inspired by venom, in safeguarding Wistar rats from chemically induced seizures. The present study evaluated the new analog from occidentalin-1202 named NOR-1202 using acute and chronic pilocarpine-induced models and an acute kainic acid (KA) male mice model. NOR-1202 was administered through the intracerebroventricular (i.c.v.), subcutaneous, or intraperitoneal routes, with stereotaxic procedures for the i.c.v. injection. In the acute pilocarpine-induced model, NOR-1202 (i.c.v.) protected against generalized seizures and mortality but lacked systemic antiepileptic activity. In the KA model, it did not prevent generalized seizures but improved survival. In the chronic TLE model, NOR-1202's ED did not differ significantly from the epileptic or healthy groups regarding time spent in spontaneous recurrent seizures during the five-day treatment. However, the NOR-1202 group exhibited more seizures than the healthy group on the second day of treatment. In summary, NOR-1202 exhibits antiepileptic effects against chemoconvulsant-induced seizures, but no effect was observed when administered systemically.
癫痫是一种以神经元过度活动和电放电同步为特征的神经障碍,是最常见的全球神经疾病之一。尽管抗癫痫药物被广泛应用,但它们常常会产生不良反应,并且在控制颞叶癫痫(TLE)患者的癫痫发作方面效果不佳。最近的研究探讨了一种名为 NOR-1202 的新型类似物的潜力,这种类似物是一种受毒液启发的肽,可保护 Wistar 大鼠免受化学诱导的癫痫发作。本研究使用急性和慢性匹罗卡品诱导模型以及急性海人酸(KA)雄性小鼠模型,评估了来自 occidentalin-1202 的新类似物 NOR-1202。NOR-1202 通过脑室内(i.c.v.)、皮下或腹腔途径给药,通过立体定向程序进行 i.c.v. 注射。在急性匹罗卡品诱导模型中,NOR-1202(i.c.v.)可预防全身性癫痫发作和死亡,但缺乏全身抗癫痫作用。在 KA 模型中,它不能预防全身性癫痫发作,但能提高存活率。在慢性 TLE 模型中,NOR-1202 的 ED 在 5 天治疗期间自发复发癫痫发作时间方面与癫痫组或健康组无显著差异。然而,NOR-1202 组在治疗的第二天比健康组发作更多。综上所述,NOR-1202 对化学惊厥诱导的癫痫发作具有抗癫痫作用,但全身给药时没有观察到效果。