Analgesic effects of diltiazem and verapamil after central and peripheral administration in the hot-plate test.

1. The analgesic effects of diltiazem and verapamil, both per se and together with morphine, were studied using subcutaneous (s.c.) and intracerebroventricular (i.c.v.) administrations, in the hot-plate test in mice. 2. The i.c.v. injection of verapamil (15-120 micrograms/mouse) and diltiazem (60-120 micrograms/mouse) induced dose-dependent analgesic effects. 3. The i.c.v. administration of verapamil (30-120 micrograms/mouse) and diltiazem (60-120 micrograms/mouse) significantly enhanced, in a dose-dependent way, the analgesic effects of morphine and produced a parallel displacement to the left of the morphine log dose-response line. 4. When these calcium channel blockers were administered subcutaneously at doses of 40 and 80 mg/kg, they exerted no analgesic actions, but dose-dependently potentiated the analgesic effects of morphine, producing a parallel shift to the left of the morphine log dose-response line. 5. These results suggest that inhibition of calcium entry through calcium channels induced by verapamil and diltiazem may play a role in analgesia development.