Species differences in the relative analgesic potencies of some classical opiates and opioid peptides.

The analgesic ED50 values of some classical morphine congeners (morphine, methadone, fentanyl, azidomorphine) in the rat and mouse tail-flick tests were found to be similar. However, several synthetic derivatives of the natural enkephalins were more potent in mice than in rats. (These analogs contain D-amino acid in position 2 and D- or L-sulfonic (or phosphonic) acid residue in position 5). beta-Endorphin, D-Met2, Pro5-enkephalinamide and two partial agonists showed intermediate interspecies relative potencies. According to the data obtained, similar opiate receptors might mediate the analgesic action of classical opiates in rats and in mice. However, the opiate receptors responsible for the antinociceptive effects of the above mentioned enkephalin analogues must be dissimilar in the two species examined. The results are discussed in terms of the role of mu- and delta-receptors in mediation of the analgesic effect induced by different types of opioids.