Anticonvulsant profile of 4-amino-(2-methyl-4-aminophenyl)benzamide in mice and rats.
An original ameltolide analogue 4-amino-(2-methyl-4-aminophenyl)benzamide, in which a second amino group has been introduced, was synthesized and evaluated for anticonvulsant activity. After intraperitoneal administration to mice, 4-amino-(2-methyl-4-aminophenyl)benzamide was found active in the maximal electroshock seizure test and against the tonic seizures elicited either by bicuculline or 3-mercaptopropionic acid. 4-amino-(2-methyl-4-aminophenyl)benzamide (4A-2M4A-PB) gave anti maximal electroshock seizures ED50 of 63 micromol/kg (15.4 mg/kg) and a TD50 of 676 micromol/kg (163 mg/kg), yielding a PI of 10.7; the potency is similar to that of the 4-amino-(2-methyl-3-aminophenyl)phthalimide (4A-2M3A-PP), superior to that of 4-amino-(2,6-dimethylphenyl)phthalimide (4A-2,6-DMPP), close to that of phenytoin and carbamazepine and inferior to that of ameltolide. 4A-2M4A-PB with an ED50 of 41[28-60] micromol/kg (9.9 mg/kg) is as active after oral administration to rats as carbamazepine, more active than ameltolide, 4-A-2M3A-PP and phenytoin and slightly less active than the 4A-2,6-DMPP. The introduction of a second amino group on the substituted phenyl ring does not affect drastically the anticonvulsant potency after intraperitoneal administration to mice; moreover, it seems to enhance the activity after oral administration. 4A-2M4A-PB is a good candidate both for further pharmacokinetic studies and for the study of the precise mechanism of action.
Kanyonyo
M R
MR
Department of Pharmaceutical Sciences, Catholic University of Louvain, Bruxelles, Belgium.
Poupaert
J H
JH
Lambert
D M
DM
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000627:therapeutic use*; D001549:Benzamides / Q000138:chemical synthesis* / Q000627:therapeutic use*; D002220:Carbamazepine / Q000627:therapeutic use; D004597:Electroshock; D008297:Male; D051379:Mice; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*
C111055:4-amino-(2-methyl-4-aminophenyl)benzamide; D000927:Anticonvulsants; D001549:Benzamides; D002220:Carbamazepine