Anticonvulsant activity and selective inhibition of NAD-dependent oxidations by 1,2,4-trisubstituted-5-imidazolones.

Nine 1-(3,4-dimethoxyphenylethyl)-2-methyl-4-(substituted benzylidene)-5-imidazolones were synthesized, characterized by their sharp melting points, elemental analyses and infrared spectra and evaluated for anticonvulsant activity. All 1,2,4-trisubstituted-5-imidazolones at a dose of 100 mg/kg i.p. possessed anticonvulsant activity and the degree of protection observed against pentylenetetrazol-induced convulsions in mice ranged from 20 to 60%. These 1,2,4-trisubstituted-5-imidazolones selectively inhibited in vitro oxidation of the nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate, alpha-ketoglutarate and NADH by rat brain homogenates while the NAD-independent oxidation of succinate remained unaltered. The anti-convulsant activity possessed by 1,2,4-trisubstituted-5-imidazolones was unrelated with their ability to selectively inhibit respiratory activity of rat brain homogenates.