Anticonvulsant activity and inhibition of respiration in rat brain homogenates by substituted trimethoxybenzamides.

Ten N-[4-[4-(arylthiosemicarbazido)carbonyl]phenyl]-3,4,5-trimethoxybenzamides were synthesized and characterized by their sharp melting points, elemental analyses, and IR and NMR spectra. All substituted benzamides were evaluated for their anticonvulsant activity. The degree of protection afforded by these compounds (100 mg/kg ip) against pentylenetetrazol (90 mg/kg sc)-induced convulsions in mice ranged from 10 to 80%. The ability of substituted benzamides to inhibit respiratory activity was observed by inhibition of oxidation of pyruvate, alpha-ketoglutarate, NADH, and succinate by rat brain homogenates. Inhibition of pyruvic acid oxidation was concentration dependent. The anticonvulsant activity of substituted benzamides was not related to their ability to inhibit cellular respiratory activity.