OPIATE ACTIVITY OF [DALA2,DELTAZPHE4]-METHIONINE-ENKEPHALINAMIDE

The opiate-like activity of [DAla2,ΔzPhe4, Met5]-enkephalinamide (ΔFE) was evaluated in the stimulated guinea pig ileum assay and the mouse tailflick test. In vitro it caused a naloxone-reversible inhibition of the electrically induced twitch at a dose about one-fifth that of [DAla2,Met5]-enkephalinamide (DAE). The ED50 for the analgesic effect of ΔFE after intracerebral injection was also approximately one-fifth that of DAE. However, ΔFE was not active after intraperitoneal injection. These data imply that some increases in the potency of enkephalin derivatives may not be entirely attributable to resistance to enzymatic degradation, but may be related to preferred structural conformation at the receptor. © 1979.