The influence of three L-type calcium channel blockers on morphine effects in healthy volunteers

Numerous animal studies and several clinical studies have shown that calcium channel blockers (CCBs) augment opioid analgesia. We sought to determine whether three CCBs from three L-type subgroups (i.e., L-CCBs) enhanced morphine analgesic effects in healthy volunteers, and whether other effects of morphine (e.g., mood-altering effects) were altered by the CCB pretreatment. We examined the effects of three L-CCBs--diltiazem (30 mg, per os [P.O.]), nimodipine (60 mg, P.O.), and verapamil (80 mg, P.O.)--on morphine (10 mg/70 kg, intravenously) effects in nine healthy volunteers. Subjects first ingested the oral drug or placebo and 120 min later were injected with morphine or saline. Dependent measures included pain ratings measured during a cold-pressor test and subjective, psychomotor, and physiological effects. The L-CCBs alone had no effect on any of the dependent measures. Morphine alone and in combination with the L-CCBs reduced pain ratings, but there were no statistically significant differences in the pain measures between the morphine alone and the L-CCB/morphine conditions. Pretreatment with the L-CCBs in most cases neither potentiated nor attenuated the other effects of morphine. L-CCBs as well as the N-type CCBs currently under drug development should continue to be investigated to determine their potential as analgesic adjuvants.

This study is important because the results are at odds with numerous animal studies and several clinical studies, which indicate that calcium channel blockers of the L-type increase the amount of analgesia produced by morphine. Using clinically relevant doses of L-type blockers, we could find no potentiation of morphine analgesia.