Comparison of tolerance development and dependence capacities of morphine, beta-endorphin, and [D-Met2, Pro5]-enkephalinamide.

The tolerance-development capacities of beta-endorphin, [D-Met2, Pro5]-enkephalinamide, and morphine were compared in rats, and the dependence capacity of morphine was compared with that of the enkephalin analogue in mice. Tolerance to the analgesic effect, as measured by the tail-flick test, developed somewhat more rapidly in the [D-Met2, Pro5]-enkephalinamide-treated group than in the others. A similar relationship was found for the dependence capacity. Considering that the enkephalin analogue displayed the strongest analgesic activity, the well-known correlation between antinociceptive and tolerance development/dependence capacities of opiates seems to be valid for opioid peptides as well.