ARTICLE AUTHOR: Bailleux-V; Vallee-L; Nuyts-JP; Hamoir-G; Poupaert-JH; Stables-JP; Vamecq-J

REPRINT AUTHOR: Vamecq, J; CHU LILLE; HOP B, N FRANCE CTR STUDY CHILDHOOD EPILEPSY, SERV PROF JEAN PIERRE NUYTS; F-59037 LILLE; FRANCE

SOURCE: EUROPEAN-JOURNAL-OF-MEDICINAL-CHEMISTRY. 1995; 30 (5) : 439-444

ABSTRACT:

A short series of 4-nitro-N-phenylbenzamides was synthesized and evaluated for anticonvulsant properties and neurotoxicity. In mice dosed intraperitoneally, three of the four 4-nitro-N-phenylbenzamides were efficient in the maximal electroshock-induced seizure (MES) test, especially N-(2,6-dimethylphenyl)-4-nitrobenzamide (EDS, value in the MES test = 31.8 mu mol/kg, TD,, = 166.9 mu mol/kg, protective index [PI] = 5.2) and N-(2-chloro-6-methylphenyl)-4-nitrobenzamide (ED(50) value in the MES test = 90.3 mu mol/kg, TD50 = 1.068 mu mol/kg, PI = 11.8). The latter 4-nitro-N-phenylbenzamide was also found to be active against seizures induced by subcutaneous pentylenetetrazole (sc Ptz) and was selected for further evaluation in rats dosed orally. In these conditions, N-(2-chloro-6-melhylphenyl)-4-nitrobenzamide was found to be, in the MES test, three times more active than phenytoin and 4-amino-N-(2,6-dimethylphenyl)benzamide, two potent anti-MES agents.