Tetrapeptide-amide analogues of enkephalin: the role of C-terminus in determining the character of opioid activity.
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Biomedical subjects
Publications and source records attributed to E Miglécz.
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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.
The in vivo equivalent of pA2 values were determined in rat tail-flick and mouse hot-plate tests for naloxone against morphine, beta-endorphin and a synthetic enkephalin analog, (D-Met2,Pro5)-enkephalinamide, as analgesics. In mice the apparent pA2 value of naloxone against morphine (6.86) was similar to that found by previously and essentially the same values were obtained against the opioid peptides, indicating homogenous receptor population for the analgesics studied. In rats the pA2 of naloxone against morphine (7.17) was lower than against either beta-endorphin (7.55) or (D-Met2,Pro5)-enkephalinamide (7.51), warning that in rats such a homogeneity of the "analgesic" receptor population as was observed for mice may not exist.
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