Comparison of Short- and Long-Acting Benzodiazepine-Receptor Agonists With Different Receptor Selectivity on Motor Coordination and Muscle Relaxation Following Thiopental-Induced Anesthesia in Mice

Abstract

In this study, we compared the effects of Type I benzodiazepine receptor–selective agonists (zolpidem, quazepam) and Type I/II non-selective agonists (zopiclone, triazolam, nitrazepam) with either an ultra-short action (zolpidem, zopiclone, triazolam) or long action (quazepam, nitrazepam) on motor coordination (rota-rod test) and muscle relaxation (traction test) following the recovery from thiopental-induced anesthesia (20 mg/kg) in ddY mice. Zolpidem (3 mg/kg), zopiclone (6 mg/kg), and triazolam (0.3 mg/kg) similarly caused an approximately 2-fold prolongation of the thiopental-induced anesthesia. Nitrazepam (1 mg/kg) and quazepam (3 mg/kg) showed a 6- or 10-fold prolongation of the anesthesia, respectively. Zolpidem and zopiclone had no effect on the rota-rod and traction test. Moreover, zolpidem did not affect motor coordination and caused no muscle relaxation following the recovery from the thiopental-induced anesthesia. However, zopiclone significantly impaired the motor coordination at the beginning of the recovery. Triazolam significantly impaired the motor coordination and muscle relaxant activity by itself, and these impairments were markedly exacerbated after the recovery from anesthesia. Nitrazepam and quazepam significantly impaired motor coordination, and the impairments were exacerbated after the recovery. These results suggest that the profile of recovery of motor coordination and muscle flaccidity after co-administration of benzodiazepine-receptor agonists and thiopental is related to the half-life and selectivity for the benzodiazepine-receptor subtypes.