Midazolam antagonizes the analgesic effect of morphine in rats

The effect of midazolam on morphine analgesia was studied in 54 rats. Analgesia was determined by measuring threshold for motor response to noxious pressure applied to the tail. Midazolam (0.5 mg/kg) decreased the morphine-induced (1 mg/kg) increase in the reaction threshold by one-half. Flumazepil (Ro 15-1788), a specific antagonist of benzodiazepines, prevented inhibition of morphine antinociception by midazolam. These findings demonstrate that midazolam partially antagonizes the analgesic effect of morphine and, in addition, that the antagonism of midazolam on morphine analgesia is mediated by benzodiazepine receptors.