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 m...

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Bibliographic Details
Published in:Pharmacological reports 2010-03, Vol.62 (2), p.273-277
Main Authors: Sun, Xian-Yu, Wei, Cheng-Xi, Deng, Xian-Qing, Sun, Zhi-Gang, Quan, Zhe-Shan
Format: Article
Language:English
Subjects:
3-mercaptopropionic acid
Animals
Anticonvulsants - pharmacology
Anticonvulsants - therapeutic use
Disease Models, Animal
Drug Safety and Pharmacovigilance
Female
isoniazid
Male
maximal electroshock
Mice
pentylenetetrazole
Pharmacotherapy
Pharmacy
Phthalazines - pharmacology
Seizures - drug therapy
Tetrazoles - pharmacology
tetrazolo[5,1-a]phthalazine
thiosemicarbazide
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Summary: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, ED50=6.8mg/ kg) and lower neurotoxicity (median toxic dose, TD50=456.4mg/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=24mg/kg) against MES-induced seizure with low neurotoxicity (TD50>4500mg/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.
ISSN:1734-1140
2299-5684
DOI:10.1016/S1734-1140(10)70266-8