title: Synthesis and anticonvulsant activity of trans- and cis-2-(2,6-dimethylphenoxy)-N-(2- or 4-hydroxycyclohexyl)acetamides and their amine analogs.
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.
authors: Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University-Medical College, Krakow, Poland.
authors: Elżbieta
authors: E
authors: Pękala
authors: Anna M
authors: AM
authors: Waszkielewicz
authors: Edward
authors: E
authors: Szneler
authors: Maria
authors: M
authors: Walczak
authors: Henryk
authors: H
authors: Marona
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D051381:Rats; D012640:Seizures / Q000188:drug therapy*
chemical_list: D000081:Acetamides; D000588:Amines; D000927:Anticonvulsants