Antagonism of morphine analgesia by prolyl-leucyl-glycinamide (MIF-1) in humans

Abstract

Prolyl-leucyl-glycinamide (MIF-1) has been observed to inhibit the analgesic effect of morphine in a series of animal studies. In the present study, the naloxone-like properties of MIF-1 were assessed in human subjects. Eight men received a capsule containing 60 mg of MIF-1 or placebo followed one hour later by a 10 mg intramuscular injection of morphine in a double-blind, crossover design at two visits 4 weeks apart. Experimental pain was induced by the cold pressor test administered 45, 75, 120 and 180 min after the morphine. Each subject recorded severity of pain on a 100 mm line scale every 5 sec during the 120 sec his foot was immersed in the cold water tank and during the 60 seconds immediately following its removal. On a third visit, baseline values were measured in the absence of morphine, MIF-1 or placebo. Analysis of variance revealed that MIF-1 resulted in significantly higher scores (less analgesia) compared with placebo when measured at 45 and 75 min after morphine during the immersion phase and during all four times the subjects were evaluated during the removal phase. The results indicate that MIF-1 can act in humans as an opiate antagonist.