RESUMEN
A series of 4-aminobenzanilides derived from ring-alkylated anilines were prepared and evaluated for anticonvulsant activity. These benzanilides were prepared in the course of studies designed to determine the relationship between the benzamide structure and anticonvulsant effects. The compounds were tested in mice against seizures induced by electroshock and metrazole (pentylenetetrazole) and in the rotorod assay for neurologic deficit. All of the 4-aminobenzanilides showed activity at doses of 300 mg/kg against maximal electroshock seizures (MES). The 4-aminobenzanilide derived from 2,6-dimethylaniline (8) was the most potent anti-MES compound with an ED50 of 2.60 mg/kg and a protective index of 5.77 (PI = TD50/ED50). The activity profile for 8 compares quite favorably with that for phenobarbital and phenytoin in the same assays.
Asunto(s)
Anilidas/uso terapéutico , Convulsiones/tratamiento farmacológico , Anilidas/síntesis química , Anilidas/toxicidad , Animales , Fenómenos Químicos , Química , Evaluación Preclínica de Medicamentos , Electrochoque , Masculino , Ratones , Pentilenotetrazol , Convulsiones/etiología , Relación Estructura-ActividadRESUMEN
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 (6) was the most potent against maximal electroshock seizures (MES): ED50 = 42.98 mg/kg; however, the N- cyclohexylbenzamide (8) 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-(alpha-methylbenzyl)-benzamide (12) 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.