Anticonvulsant activity of some 4-methoxy- and 4-chlorobenzanilides

Article abstract of DOI:10.1002/jps.2600790308

A series of mono-, di-, and trimethylated derivatives of 4-chloro- and 4-methoxybenzanilide was synthesized and evaluated for anticonvulsant activity. This series was prepared in the course of studies designed to examine the relationship between anticonvulsant effects and benzamide structure. The compounds were tested in mice against seizures induced by maximal electroshock (MES) and pentylenetetrazole (scMet), as well as with the rotorod assay for neurologic deficit. In mice dosed intraperitoneally, 4-methoxy-2, 6-dimethylbenzanilide (4) showed a median anticonvulsant potency (ED₅₀) of 18.58 mg/kg in the MES test and a median toxicity (TD₅₀) of 133.72 mg/kg in the rotorod toxicity assay, yielding a protective index (PI = TD₅₀/ED₅₀) of 7.2. In mice dosed orally with 4, the anti-MES ED₅₀ was 27.40 mg/kg and the TD₅₀ dose was determined to be 342.58 mg/kg, resulting in a protective index of 12.5.