A series of novel schiff bases of 3-aminomethyl pyridine have been synthesized through condensation reaction with substituted aryl aldehydes/ketones and/cyclic ketones. These schiff bases were screened for anticonvulsant activity. The chemical structures of synthesized compounds were confirmed by FT-IR, 1 H-NMR, spectroscopy, and elemental analysis. A number of compounds were observed to exhibit seizures protection after intraperitoneal administration at the dose 30 and 100 mg kg-1 in various models employed. In MES screen we found five potent compounds i.e., (1c) N-(2-chlorobenzylidene) (pyridin-3-yl) methanamine, (1f) 2-methoxy-4-{(pyridine-3-ylmethyl imino) methyl} phenol, (2a) N-(3phenylallylidene) (pyridin-3-yl) methanamine, (3b) 3-{1-(pyridin-3-ylmethylimino) ethyl} benzenamine, and (4a) N-(diphenyl-methylene) (pyridin-3 yl) methanamine, emerged as most active compounds in series (ED50) 11.70, 6.39, 11.70, 8.64, and 9.13 mg kg-1 with high protective index (PI) [10. Four compounds (1e) 4-{(Pyridine-3-ylmethylmino) methyl}benzene-1,3-diol, (1g) N-(3,4,-dimethoxybenzylidene) (pyridin-3-yl)methanamine, (2b) N-{(1H-indol-3-yl)methylene}(pyridin-3-yl) methanamine, and (5) N-cyclohexylidene (pyridine-3-yl) methanamine) showed remarkable protection over clinically used drugs in sc.PTZ screen (ED50) 6.44, 11.70, 6.47, and 14.16 with (PI [10). Compound (4b) showed good anticonvulsant activity (ED50) 20.79, but with relatively higher neurotoxicity (PI, 0.57). Compound (1e) was active in both sc.PTZ and in sc.STR seizures. Some selected compounds were subjected to oral MES screen (30 mg kg-1 ) in rats, most of the compounds showed peak activity after 0.5 h of oral administration.