Liao Ai-Mei, Wang Tiantian, Cai Bangrong, Jin Yi, Cheon Seunghoon, Chun ChangJu, Wang Zengtao
Research Institute of Drug Development, College of Pharmacy, Chonnam National University, 77 Yongbong-ro, Buk-Gu, Gwangju, 61186, Republic of Korea.
School of life Science, Hefei Normal University, Hefei, 230601, China.
Arch Pharm Res. 2017 Apr;40(4):435-443. doi: 10.1007/s12272-016-0881-y. Epub 2016 Dec 31.
A series of 5-substituted 1-H-tetrazoles were designed and synthesized as potent anticonvulsant agents. Their preliminary anticonvulsant activities were evaluated using maximal electroshock and subcutaneous pentylenetetrazole (scPTZ) seizure tests. Neurotoxicity was determined using rotarod test. The results indicated that the compound 2j in scPTZ model exhibited the ED values of 83.3 mg/kg, superior to the standard drug ethosuximide with the maximum activity. In addition, compound 2k showed the most potent activity in MES model with ED value of 9.6 mg/kg and TD value of 189.5 mg/kg after intraperitoneal injection in mice, and displayed a high protective index (TD/ED) of 19.7 compared to reference antiepileptic drugs.
设计并合成了一系列5-取代的1-H-四唑作为有效的抗惊厥剂。使用最大电休克和皮下注射戊四氮（scPTZ）惊厥试验评估了它们的初步抗惊厥活性。使用转棒试验测定神经毒性。结果表明，化合物2j在scPTZ模型中表现出的ED值为83.3mg/kg，优于具有最大活性的标准药物乙琥胺。此外，化合物2k在小鼠腹腔注射后的MES模型中表现出最有效的活性，ED值为9.6mg/kg，TD值为189.5mg/kg，与参考抗癫痫药物相比显示出19.7的高保护指数（TD/ED）。
