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

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.