Sun Xian-Yu, Wei Cheng-Xi, Deng Xian-Qing, Sun Zhi-Gang, Quan Zhe-Shan
College of Pharmacy, Yanbian University, Jilin, PR China.
Arzneimittelforschung. 2010;60(6):289-92. doi: 10.1055/s-0031-1296289.
A new series of 6-alkyoxyl-tetrazolo[5,1-a] phthalazine derivatives (4 a-4 o) were synthesized as potential anticonvulsant agents. Anticonvulsant activity was evaluated by the maximal electroshock (MES) test. Neurotoxicity was evaluated by the rotarod neurotoxicity test. The pharmacological results showed that 6-(4-chlorophenyoxyl)-tetrazolo[5,1-a]phthalazine (4 m) was the most potent agent, with a median effective dose (ED50) of 6.8 mg/kg and a median neurotoxic dose (TD50) of 456.4 mg/kg. The protective index (PI = TD50/ED50) for compound 4 m was 67.1, which was significantly higher than that for the reference drug carbamazepine (PI = 6.4).
合成了一系列新型的6-烷氧基-四唑并[5,1-a]酞嗪衍生物（4a - 4o）作为潜在的抗惊厥剂。通过最大电休克（MES）试验评估抗惊厥活性。通过转棒神经毒性试验评估神经毒性。药理结果表明，6-(4-氯苯氧基)-四唑并[5,1-a]酞嗪（4m）是最有效的药物，其半数有效剂量（ED50）为6.8mg/kg，半数神经毒性剂量（TD50）为456.4mg/kg。化合物4m的保护指数（PI = TD5 / ED50）为67.1，显著高于参比药物卡马西平（PI = 6.4）。
