The agonist and antagonist properties of N-allylenkephalins

The agonist (ID 50) and antagonist (Ke) potencies of the newly synthesized N-allyl derivatives of Met5-enkephalin and Leu5-enkephalin were compared with those of their respective parent compounds on the myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum. N-allyl substitution of the aminenitrogen in the Met5-enkephalin significantly decreased both the ID 50 and the Ke. In contrast, similar substitution in Leu5-enkephalin did not significantly alter the ID50, but caused an almost tenfold increase in the Ke. The results suggest that substitution on the amine-nitrogen of Leu5-enkephalin rather than Met5-enkephalin is more likely to produce potent narcotic antagonists.