New derivatives of benzylamide with anticonvulsant activity.
Previously obtained picolinic acid benzylamide is a potent anticonvulsant with low neurotoxicity. In search for new effective anticonvulsants twelve new benzylamides (1-12) were synthesized and preliminary evaluated in the Anticonvulsant Screening Program (ASP) of Antiepileptic Drug Development Program (ADDP) of NIH. Two of them appeared the most promising: 1-cyclopentenecarboxylic acid benzylamide (1-Cpc-BZA) (9) showed MES ED50 = 85,36 mg/kg (PI = 2,49), scPTZ ED50 = 1,37 mg/kg (PI = 1,37), 6Hz-EST ED50 = 50,29 mg/kg and cyclopentanecarboxylic acid benzylamide (Cpc-BZA) (11) showed pilocarpine ED50 = 154.75 mg/kg and pilocarpine ED97 = 270.95 mg/kg.
Strupińska
Marzanna
M
Department of Drug Chemistry, Medical University of Warsaw, 02-097 Warszawa, Poland.
Rostafińska-Suchar
Grazyna
G
Stables
James P
JP
Paruszewski
Ryszard
R
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D003292:Convulsants; D004597:Electroshock; D051379:Mice; D018721:Muscarinic Agonists / Q000494:pharmacology; D020258:Neurotoxicity Syndromes / Q000523:psychology; D010433:Pentylenetetrazole; D010862:Pilocarpine / Q000037:antagonists & inhibitors; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000209:etiology
D000927:Anticonvulsants; D001549:Benzamides; D003292:Convulsants; D018721:Muscarinic Agonists; D010862:Pilocarpine; D010433:Pentylenetetrazole