[Rational conception, synthesis and evaluation of phenytoinergic potential anticonvulsants. A series ofretrobenzamides: N-(nitrophenyl) benzamides and N-(aminophenyl) benzamides].
Retrobenzamides [N-(nitrophenyl) benzamides and N-(aminophenyl)benzamides] were developed in the perpective of a design for phenytoinergic agents. Anticonvulsant and neurotoxic properties of these compounds were evaluated in mice and rats in two seizure models (maximal electroshock-induced seizures [MES] and seizures induced by subcutaneous administration of pentylenetetrazole [scPtz]) and in the rotorod test. Data obtained were compared with those recorded on carbamazepine and phenytoin (antiepileptic drugs widely utilized in human clinics), ameltolide (anticonvulsant compound recently developed by Eli Lilly in human clinical trials) and other compounds previously reported by our research group. Studies on retrobenzamides in mice administered by intraperitoneal route point out a good anticonvulsant potential in the MES test for the amino derivatives (N-(aminophenyl)benzamides) and moderate activity in the case of the corresponding "nitro" derivatives. In rats dosed orally, aminoretrobenzamides were less active in the MES test than in mice dosed intraperitoneally.
Bourhim
M
M
INSERM Lab Ext, Domaine du CERTIA, Villeneuve d'Ascq, France.
Kanyonyo
M D
MD
Lambert
D M
DM
Poupaert
J H
JH
Stables
J P
JP
Vamecq
J
J
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D051379:Mice; D010672:Phenytoin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats
D000927:Anticonvulsants; D001549:Benzamides; D010672:Phenytoin