Evaluation of the anticonvulsant activity of 6-(4-chlorophenyoxy)-tetrazolo[5,1-a]phthalazine in various experimental seizure models in mice |
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Authors: | Xian-Yu Sun Cheng-Xi Wei Xian-Qing Deng Zhi-Gang Sun Zhe-Shan Quan |
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Institution: | 1. Affiliated Hospital of Inner Mongolia University for the Nationalities, No. 1742, HuoLinHe Street, Tongliao, Neimenggu, 028050, China;2. College of Pharmacy, Yanbian University, No. 1829, JuZi Street, Yanji, Jilin, 133000, China |
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Abstract: | This study investigated the anticonvulsant activity of a new phthalazine tetrazole derivative, QUAN-0808 (6-(4-chlorophenoxy)-tetrazolo5,1-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, ED50 = 6.8 mg/ kg) and lower neurotoxicity (median toxic dose, TD50 = 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 (ED50 = 24 mg/kg) against MES-induced seizure with low neurotoxicity (TD50 > 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. |
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Keywords: | tetrazolo[5 1-a]phthalazine maximal electroshock pentylenetetrazole isoniazid thiosemicarbazide 3-mercaptopropionic acid |
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