Magnitude of acute tolerance to opioids is not related to their potency

It was suggested that for a given analgesic effect, more potent opioids may produce smaller degrees of tolerance than those with lower analgesic potency. The use of opioids with high analgesic potency to reduce the rate of tolerance development would be an important therapeutic consideration. This study tested the hypothesis that the degree of acute tolerance to the analgesic effect of opioids is inversely related to their potency. In the experiments on rats, the analgesic effects of morphine, alfentanil, and sufentanil given by a continuous 8-h infusion at a constant rate, were determined by measuring the threshold of motor response to noxious pressure on the tail. The comparative degree of acute tolerance was determined on the basis of the decline in the level of analgesia at the end of the infusion period. Morphine 4 mg.kg-1.h-1, alfentanil 0.45 mg.kg-1.h-1, and sufentanil 0.0085 mg.kg-1.h-1 caused approximately similar increases in the pain threshold. The peak of analgesia could not be maintained; it declined by 74 +/- 6% (P less than 0.0001) with morphine, 86 +/- 6% (P less than 0.0001) with alfentanil, and 92 +/- 2% (P less than 0.0001) with sufentanil. The results indicate that the infusion of alfentanil and sufentanil, which differ from morphine by higher analgesic potency (by 10-fold and more than 100-fold, respectively), results in a decline in the degree of analgesia during infusion similar to that of morphine. These data reject the hypothesis that the magnitude of acute tolerance to the analgesic action of opioid drugs following their systemic administration is inversely related to their potency.