Anticonvulsant and antiepileptogenic effects of azolylchromanones on lithium–pilocarpine induced seizures and pentylenetetrazole-kindling model of epilepsy

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• 作者：Abbas Kebriaeezadeh ; Saeed Emami ; Mohsen Ebrahimi ; Mohammad Sharifzadeh ; Reza Khorasani ; Abbas Shafiee
• 关键词：Anticonvulsant ; Kindling ; Lithium– ; pilocarpine ; Azole ; Chroman-4-one
• 刊名：Biomedicine and Pharmacotherapy
• 出版年：2008
• 出版时间：April-May 2008
• 年：2008
• 卷：62
• 期：4
• 页码：208-211
• 全文大小：159 K

文摘

Recently, we described the design and synthesis of azolylchroman derivatives as conformationally constrained analogs of (arylalkyl)azole anticonvulsants. In the present study, two distinct pharmacological models, lithium–pilocarpine induced seizure and PTZ-induced kindling were used to investigate both anticonvulsive and antiepileptogenic properties of the selected azolylchromanones including 7-chloro-3-(1H-imidazol-1-yl)chroman-4-one (I), 3-(1H-1,2,4-triazol-1-yl)chroman-4-one (II), trans-3-(1H-imidazol-1-yl)-2-methylchroman-4-one (III) and trans-7-chloro-3-(1H-imidazol-1-yl)-2-methylchroman-4-one (IV). Although compounds I and II were highly effective at the dose of 5 mg/kg against acute PTZ-induced convulsions as previously reported by us, these compounds exhibited limited effects in PTZ-induced kindling model. However, compound I was found to exert respectable action in delaying seizures and reducing seizure index at the dose of 10 mg/kg. In contrast, all tested compounds showed an anticonvulsant effect due to the considerably delayed onset of seizures in lithium–pilocarpine model. Compound I exhibited more effective action in delaying seizures as well as decreasing seizure duration in this model of epilepsy. In conclusion, the azolylchromanones I–IV, especially 7-chloro-3-(1H-imidazol-1-yl)chroman-4-one (I), were effective against lithium–pilocarpine induced status epilepticus, suggesting the potential application of the test compounds in the treatment of status epilepticus.