Temporal variation in the interaction between calcium channel blockers and morphine-induced analgesia.

Circadian variations in the interaction between calcium channel blockers and morphine-induced analgesia were determined by the mouse hot-plate test. Calcium channel blockers diltiazem, verapamil, or nicardipine alone did not display any significant analgesic effect, but all of them potentiated morphine-induced analgesia when injected 30 min prior to morphine at most of the injection times. In terms of percent absolute potentiation, they produced more potentiation during the light period than darkness. Their potentiating effects decreased abruptly during darkness, and around the midtime of the dark period no significant potentiation of morphine-induced analgesia was observed. It is concluded that these fluctuations in the magnitude of interaction between calcium channel blockers and morphine must be taken into consideration particularly in studies dealing with the role of calcium in analgesia.