Interaction of the competitive AMPA receptor antagonist NBQX with hexobarbital

IP administration of hexobarbital to rats caused a mean sleeping time of 93.6 min (SD 21.5). IV infusion of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo( f)quinoxaline (NBQX) at a dose rate of 0.11 mg/kg/min starting 30 min after administration of hexobarbital prolonged the mean sleeping time to 132.2 min (SD 14.9). Dose rates of 0.33 and 1.10 mg/kg/min prolonged the mean sleeping times to 176.4 min (SD 33.3) and 444.1 min (SD 72.0), respectively. Measured 180 and 450 min after the start of the study, there were no differences in the plasma concentrations of hexobarbital in groups receiving hexobarbital alone compared to groups receiving the high-dose rate of NBQX starting 30 min after administration of hexobarbital. The present results demonstrate that by IV infusion NBQX dose dependently prolonged the sleeping time of hexobarbital. There were no indications of interactions on hexobarbital elimination of either isomer. It is therefore likely that NBQX acts synergistically with hexobarbital to depress the central nervous activity.