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

Abstract

The effect of alkylpyrazine derivatives on pentobarbital-induced sleeping time, picrotoxicin-induced convulsion and gamma-aminobutyric acid (GABA) levels in mouse brain were studied. The duration of pentobarbital-induced sleep in mice was dose-dependently increased by 2,5-dimethylpyrazine (DMP). The duration of pentobarbital-induced sleep was also increased by an administration route of intracerebroventricular injection. Sleep duration was also increased by the administration of isomers of DMP, 2-chloro-3,6-dimethylpyrazine (DMP-Cl) and 2-fluoro-3,6-dimethylpyrazine (DMP-F), but 3,6-dimethylpyrazine-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 combination with aminooxyacetic acid (AOAA) and diazepam compared to a single injection. 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 increased 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.