ENHANCED ANTIOPIATE ACTIVITY AND ENZYME RESISTANCE IN PEPTIDOMIMETICSOF FMRFAMIDE CONTAINING (E)-2,3-METHANOMETHIONINE

FMRFamide is a molluscan peptide that has shown antiopiate activity in a number of mammalian test systems. The current study determined the antiopiate potency of FMRFamide and two conformationally constrained p eptidomimetics of FMRFamide containing stereoisomers of (E)-2,3-methan omethionine. Morphine abstinence signs were observed after varying dos es (0.25-25.0 mug) of these substances were injected into the third ve ntricle of morphine-dependent rats. Both peptidomimetics were far more potent than FMRFamide itself. In addition, although both peptidomimet ics bound with lower affinity than FMRFamide to rat spinal cord recept ors for NPFF (the mammalian FMRFamide-like peptide), they were far mor e resistant than FMRFamide to enzymatic degradation by leucine aminope ptidase.