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.
Kebriaeezadeh
Abbas
A
Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Emami
Saeed
S
Ebrahimi
Mohsen
M
Sharifzadeh
Mohammad
M
Khorasani
Reza
R
Shafiee
Abbas
A
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000188:drug therapy*; D007696:Kindling, Neurologic / Q000187:drug effects; D018021:Lithium Chloride / Q000633:toxicity; D008297:Male; D051379:Mice; D010433:Pentylenetetrazole; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000188:drug therapy*
D000927:Anticonvulsants; D010862:Pilocarpine; D018021:Lithium Chloride; D010433:Pentylenetetrazole