Opiate receptor-binding activity of [D-Thr2,Thz5]-and [D-Met2,Thz5]-enkephalinamides

The binding characteristics of two highly potent analgesic enkephalin analogs, [D-Thr2, Thz5]-and [D-Met2, Thz5]-enkephalinamide, to the rat brain membrane preparation have been investigated using tritiated Leu-enkephalin, human beta-endorphin or dihydromorphine as the primary ligand. Concentrations for 50% inhibiting activity of the enkephalin analogs are much lower in displacing tritiated dihydromorphine in comparison with that for the other two tritiated ligands. In addition, a correlation between analgesic potency and capacity to displace tritiated dihydromorphine is observed. These data may explain the high antinociceptive activity of the enkephalin analogs and support the hypothesis that the mu-receptor is involved with analgesia.