Analgesic effects of several calcium channel blockers in mice.

The possibility that calcium channel blockers might produce antinociception and increase morphine analgesia was examined using the acetic acid writhing test in mice. Subcutaneous injections of diltiazem, verapamil, nicardipine, flunarizine and cinnarizine produced a dose-dependent antinociception. This activity of diltiazem was stereospecific; d-cis-diltiazem was more potent than 1-cis-diltiazem. All the calcium channel blockers studied increased morphine analgesia and displaced to the left the morphine dose-response curve. This effect of diltiazem was also stereospecific. These results suggest that calcium channel blockers can induce analgesia and increase morphine analgesia, possibly through a decrease in cellular calcium availability.