Anticonvulsant activity of some 4-aminobenzamides

Article abstract of DOI:10.1021/jm00372a013

A series of 4-aminobenzamides of some simple primary and secondary amines were prepared and evaluated for anticonvulsant effects. The compounds were tested in mice against seizures induced by electroshock and pentylenetetrazole (metrazole) and in the rotorod assay for neurologic deficit. For those N-alkyl amides tested, 4-amino-N-amylbenzamide was the most potent against maximal electroshock seizures (MES): ED50=42.98 mg/kg; however, the N-cyclohexylbenzamide showed the greatest protective index (PI=TD50/ED50), 2.8. The introduction of a second aromatic ring produced more potent compounds, with d,l-4-amino-N-(α-methylbenzyl)-benzamide showing the highest level of activity. This compound has an anti-MES ED50 of 18.02 mg/kg in mice when administered intraperitoneally (ip) and a TD50 of 170.78 mg/kg (PI=9.5) in the same species. These data compare quite favorably with those for phenobarbital and phenytoin in the same assays.