Evaluation of the anticonvulsant activity of 6-(4-chlorophenyoxy)-tetrazolo[5,1-a]phthalazine in various experimental seizure models in mice.
This study investigated the anticonvulsant activity of a new phthalazine tetrazole derivative, QUAN-0808 (6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine), in the mouse maximal electroshock (MES) seizure model. The neurotoxicity of QUAN-0808 was investigated using the rotarod neurotoxicity test in mice. QUAN-0808 exhibited higher activity (median effective dose, ED(50) = 6.8 mg/kg) and lower neurotoxicity (median toxic dose, TD(50) = 456.4 mg/kg), resulting in a higher protective index (PI = 67.1) compared with carbamazepine (PI = 6.4). In addition, QUAN-0808 exhibited significant oral anticonvulsant activity (ED(50) = 24 mg/kg) against MES-induced seizure with low neurotoxicity (TD(50) > 4500 mg/kg) in mice, resulting in a PI value of more than 187.5. QUAN-0808 was also tested in chemically induced animal models of seizure (pentylenetetrazole [PTZ], isoniazid [ISO], thiosemicarbazide [THIO] and 3-mercaptopropionic acid [3-MP]) to further investigate the anticonvulsant activity; QUAN-0808 produced significant anticonvulsant activity against seizures induced by ISO, THIO and 3-MP.
Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao, Neimenggu, China.
Xian-Yu
XY
Sun
Cheng-Xi
CX
Wei
Xian-Qing
XQ
Deng
Zhi-Gang
ZG
Sun
Zhe-Shan
ZS
Quan
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D010793:Phthalazines / Q000494:pharmacology*; D012640:Seizures / Q000188:drug therapy*; D013777:Tetrazoles / Q000494:pharmacology*
C552309:6-(4-chlorophenoxy)tetrazolo(5,1-a)phthalazine; D000927:Anticonvulsants; D010793:Phthalazines; D013777:Tetrazoles