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Anticonvulsant profile of 4-amino-(2-methyl-4-aminophenyl)benzamide in mice and rats.

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Kanyonyo, M R Poupaert, Jacques [UCL] Lambert, Didier [UCL]

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.

Document type Article de périodique (Journal article) – Journal Article, Research Support, Non-U.S. Gov't
Publication date 1998
Journal information "Pharmacology & toxicology" - Vol. 82, no. 1, p. 47-50 (1998)
issn 0901-9928
Publication status Publié
Affiliation UCL - MD/FARM - Ecole de pharmacie
MESH Subject Animals ; Anticonvulsants - chemical synthesis - therapeutic use ; Benzamides - chemical synthesis - therapeutic use ; Carbamazepine - therapeutic use ; Electroshock ; Male ; Mice ; Rats ; Seizures - chemically induced - drug therapy
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Bibliographic reference Kanyonyo, M R ; Poupaert, Jacques ; Lambert, Didier. Anticonvulsant profile of 4-amino-(2-methyl-4-aminophenyl)benzamide in mice and rats.. In: Pharmacology & toxicology, Vol. 82, no. 1, p. 47-50 (1998)
Permanent URL http://hdl.handle.net/2078.1/24218