Effect of alkylpyrazine derivatives on the duration of pentobarbital-induced sleep, picrotoxicin-induced convulsion and gamma-aminobutyric acid (GABA) levels in the mouse brain

The effect of alkylpyrazine derivatives on pentobarbital-induced sleeping t ime, picrotoxicin-induced convulsion and gamma -aminobutyric acid (GABA) le vels in mouse brain were studied. The duration of pentobarbital-induced ste ep in mice was dose-dependently increased by 2,5-dimethylpyrazine (DMP). Th e duration of pentobarbital-induced sleep was also increased by an administ ration route of intracerebroventricular injection. Steep duration was also increased by the administration of isomers of DMP, 2-chloro-3,6-dimethylpyr azine (DMP-Cl) and 2-fluoro-3,6-dimethylpyrazine (DMP-F), but 3,6-dimethylp yrazine-2-thiol (DMP-SH) did not affect sleep duration. The interval until the appearance of picrotoxicin-induced convulsion was prolonged by DMP and DMP-Cl. Increased sleep duration was obtained by administering DMP in combi nation with aminooxyacetic acid (AOAA) and diazepam compared to a single in jection. The interval until convulsion due to picrotoxin was also prolonged by the administration of DMP combined with diazepam and valproic acid (VPA ). The interval until the appearance of bicuculline-induced convulsion was also prolonged by pretreatment with DMP The GABA level in mouse brain was i ncreased by the administration of AOAA, VPA, DMP and DMP-Cl. These results suggest that DMP and other derivatives may strengthen the GABAnergic system in the brain.