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,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. © 2010 by institute of pharmacology polish academy of sciences.