Bailleux, V.
Vallee, L.
Nuyts, JP.
Vamecq, J.
The anticonvulsant potential of a series of N-phenylphthalimide derivatives has been screened in subcutaneous pentylenetetrazole seizure (scPTZ) and maximal electroshock seizure (MES) tests. Intraperitoneal 4-amino-N-phenylphthalimides were the most potent agents against MES in mice. Referring to the N-(2,6-dimethyl-phenyl)phthalimide structure, the order of anticonvulsant activity appears to correspond to the phthalimide ring substitution pattern of 4-amino > 4-nitro > 4-methyl; H > 3-nitro; 3-amino. The 4-amino-N-(2-methylphenyl)-phthalimide displays an anti-MES ED(50) of 47.61 mu mol/kg with a protective index (PI) of 4.2.
Oral administration to rats of the compounds found to be active in mice showed that the 4-amino-N-(2,6-dimethylphenyl)phthalimide is the most potent anti-MES agent in rats, exhibiting an ED(50) of 25.2 mu mol/kg and a PI greater than 75. Regarding the nature of the 2 and 6 substituents of the N-phenyl ring, the anticonvulsant efficiencies may be ordered as follows: 2,6-dimethyl > 2-methyl > 2-ethyl > 2-ethyl-6-methyl > 2,6-diethyl > unsubstituted phenyl ring.
N-Phenylphthalimide derivatives seem to have great potential as candidate anticonvulsant drugs.
Bibliographic reference |
Bailleux, V. ; Vallee, L. ; Nuyts, JP. ; Vamecq, J.. Synthesis and Anticonvulsant Activity of Some N-phenylphthalimides. In: Chemical & Pharmaceutical Bulletin, Vol. 42, no. 9, p. 1817-1821 (1994) |
Permanent URL |
http://hdl.handle.net/2078.1/48697 |