Use of a novel method for investigating muscle relaxant drugs: The effects of clobazam and 1,4-benzodiazepines on morphine-induced rigidity

Abstract

The aim of the study was to investigate antagonism of the rigidity produced by morphine in rats as a potential method for examining the muscle relaxant properties of benzodiazepines. The force required to displace the hind limbs by 1 cm was measured with an apparatus that was developed for measuring drug-induced changes in the limb muscle tone of conscious, lightly restrained rats. Neither diazepam nor clobazam alone, in doses up to 3 mg/kg Intraperitoneal (IP), had any effects on limb muscle tone. Morphine (7.5 mg/kg) caused a rapid-onset, sustained rigidity, which was partly reversed by diazepam at doses (0.2–0.5 mg/kg) that did not greatly potentiate morphine-induced respiratory depression. In contrast, clobazam (0.2–0.5 mg/kg) had no effect on morphine rigidity. Several other 1,4-benzodiazepines were tested in low doses. Both temazepam and lorazepam partly reversed morphine-induced rigidity, whereas chlordiazepoxide, flurazepam, and clonazepam had no effect. It is concluded that antagonism of morphine rigidity might provide a sensitive method for comparing muscle relaxant properties of benzodiazepines.