Anticonvulsant profile of 4-amino-(2-methyl-4-aminophenyl)benzamide in mice and rats.
Kanyonyo MR, Poupaert JH, Lambert DM
Department of Pharmaceutical Sciences, Catholic University of Louvain, Bruxelles, Belgium.
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.
PMID: 9527647, UI: 98139346