Add time:08/21/2019         Source:sciencedirect.com

A series of fifteen N-phenylphthalimides including 12 4-amino- N-phenylphthalimides and three N-(3-amino-2-methylphenyl)phthalimides was prepared and evaluated for anticonvulsant properties. The compounds were tested against seizures induced by electroshock (MES) and pentylenetetrazol (scPTZ) in mice dosed intraperitoneally. Their neurologic toxicity was assessed using the rotorod assay procedure. The most potent 4-amino-N-phenylphthalimides against MES were those possessing small lipophilic groups in either 2 or 2 and 6 positions of the N-phenyl ring. They also exhibited some activity against scPTZ and were the most toxic of the series. By contrast, no activity against scPTZ or neurotoxicity could be observed up to 300 mg/kg for members of the N-(3-amino-2-methylpheryl)phthalimide series. In this series, the order of anti-MES activity appears to correspond to the phthalimide ring substitution pattern of 4-amino >; H >; 4-methyl. Quantitation of anticonvulsant properties and toxicity of 4-amino-N-(2,6-dimethylphenyl)phthalimide (ADD 213063) previously initiated in rats has been, here, extended to mice dosed intraperitoneally but also orally. The confrontation of the two modes of administration in mice suggests that ADD 213063 presents with a good bioavailability.

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