A new homologous series of anticonvulsants: phenyl alcohol amides. Synthesis and pharmacological evaluation.
The anticonvulsant activity of a homologous series of phenyl alcohol amides is described. (+-)-2-Hydroxy-2-phenylbutyramide (1), (+-)-3-hydroxy-3-phenylpentanamide (2) and (+-)-4-hydroxy-4-phenylhexanamide (3) were prepared and tested for their anticonvulsant profile and neurotoxicity. 1, 2 and 3 exhibited a broad profile of anticonvulsant activity and a similar significant activity in the seizures provoked by maximal electroshock, pentetrazol, 4-aminopyridine, bicuculline and thiosemicarbazide, but in the strychnine and picrotoxin tests, the protection was variable. The rotarod ataxia test was used to evaluate their neurotoxicity. In this test 2 possesses the lowest neurotoxicity.
Meza-Toledo
S E
SE
Departamento de Bioquímica, Escuela Nacional de Ciencias Biológica, Instituto Politécnico Nacional (IPN), Mexico City, Mexico.
Zenteno-García
M T
MT
Juárez-Carvajal
E
E
Martínez-Muñoz
D
D
Carvajal-Sandoval
G
G
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004597:Electroshock; D006880:Hydroxy Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D010654:Phenylbutyrates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004856:Postural Balance / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control
D000577:Amides; D000927:Anticonvulsants; D006880:Hydroxy Acids; D010654:Phenylbutyrates; C068957:3-hydroxy-3-phenylpentamide; C068956:2-hydroxy-2-phenylbutyramide; C020361:gamma-hydroxy-gamma-ethyl-gamma-phenylbutyramide