Synthesis and primary anticonvulsant activity evaluation of 6-alkyoxyl-tetrazolo [5,1-a]phthalazine derivatives.
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).
Sun
Xian-Yu
XY
College of Pharmacy, Yanbian University, Jilin, PR China.
Wei
Cheng-Xi
CX
Deng
Xian-Qing
XQ
Sun
Zhi-Gang
ZG
Quan
Zhe-Shan
ZS
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000627:therapeutic use*; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D010793:Phthalazines / Q000138:chemical synthesis / Q000627:therapeutic use*; D045442:Rotarod Performance Test; D012640:Seizures / Q000188:drug therapy*; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D010793:Phthalazines