Anticonvulsant activity of some 4-aminobenzamides.

Abstract

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.

• Authors: C R Clark, M J Wells, R T Sansom, G N Norris, R C Dockens, W R Ravis
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 27 Issue 6 Pg. 779-82 (Jun 1984) ISSN: 0022-2623 [Print] United States
• PMID: 6737420 (Publication Type: Journal Article)

Chemical References

• Anticonvulsants
• Benzamides
• Pentylenetetrazole
• Bicuculline

Topics

• Animals
• Anticonvulsants (chemical synthesis)
• Benzamides (chemical synthesis, pharmacology)
• Bicuculline (pharmacology)
• Electroshock
• Male
• Mice
• Pentylenetetrazole (pharmacology)
• Seizures (chemically induced)