Synthesis and anticonvulsant activity of trans- and cis-2-(2,6-dimethylphenoxy)-N-(2- or 4-hydroxycyclohexyl)acetamides and their amine analogs |
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Authors: | Pękala Elżbieta Waszkielewicz Anna M Szneler Edward Walczak Maria Marona Henryk |
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Institution: | Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University-Medical College, Krakow, Poland. |
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Abstract: | A group of trans- and cis-2-(2,6-dimethylphenoxy)-N-(2-hydroxycyclohexyl)acetamides (1-7) and -ethylamines (8-9) have been synthesized and investigated for their anticonvulsant activity. One of them, racemic trans-2-(2,6-dimethylphenoxy)-N-(2-hydroxycyclohexyl)acetamide proved to be the most effective in MES (mice, ip), exhibiting ED(50)=42.97 mg/kg b.w. and TD(50)=105.67 mg/kg b.w. It also proved protection in focal seizures (electric kindling, rats, ip) and it raises seizure threshold. The mechanism of action is inhibition of voltage-gated sodium currents and enhancement of GABA effect. Safety pharmacology assay on threshold tonic extension revealed no lowering of the seizure threshold. |
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