Interactions between verapamil and morphine on physiological parameters in rats.

Effects of s.c. doses of morphine and verapamil, alone and in combination, on arterial blood gases and pH, mean blood pressure and heart rate were assessed in partially restrained, awake Fischer-344 rats. As expected, morphine (4-16 mg/kg) produced a dose-dependent respiratory depression, as indicated by hypoxia, hypercapnia and acidosis. Verapamil, a calcium channel antagonist, alone (10 mg/kg) did not affect these parameters; however, it significantly attenuated and delayed the aforementioned effects of morphine. Morphine caused a slight increase in mean blood pressure, which was not dose dependent, whereas verapamil reduced blood pressure dramatically even in the presence of morphine. All groups showed some tachycardia, but rats treated with morphine alone showed the most pronounced increase in heart rate, which was antagonized by verapamil. The authors conclude that the interaction of verapamil with morphine's respiratory depressant effects differs from the previously reported potentiation of morphine's antinociceptive and hypothermic actions.