Opiate receptor binding affinities of some D-amino acid substituted β-casomorphin analogs

Claus Liebmann, Maria Szücs, Klaus Neubert, Bianka Hartrodt, Helmut Arold, Alfred Barth

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19 Citations (Scopus)


β-Casomorphin-(5) and some analogs modified by the introduction of some D-amino acids and D-pipecolic acid as well as by C-terminal amidation were tested for their affinities to mu- and delta-binding sites in rat brain membranes. The binding affinities of these compounds are compared with the known activities in the guinea pig ileum (GPI) and mouse vas deferens (MVD) test and their antinociceptive potencies in rats. The substitution of D-proline for proline in position 4 in β-casomorphin-(5) and β-casomorphin-(4)amide (morphiceptin) results in derivatives with very high mu-binding affinity and mu-selectivity. These affinities correspond to the respective analgesic potencies. Both binding to mu-receptors and analgesic potency are also enhanced by the introduction of D-Phe in position 3. Testing D-Ala2 substituted derivatives with respect to their ability to compete for 3H-naloxone, we observed apparent differences between the pentapeptide amides (biphasic displacement curves) and the tetrapeptide amides (monophasic displacement curves). The substitution of L-Pro2 by D-pipecolic acid yields an analog with preferential delta-receptor affinity in the organ preparations (MVD) but preferential mu-receptor affinity in brain membranes. This finding suggests a possible difference between peripheral and central mu-binding sites.

Original languageEnglish
Pages (from-to)195-199
Number of pages5
Issue number2
Publication statusPublished - Jan 1 1986


  • Binding studies
  • D-Amino acids
  • Multiple opiate receptors
  • β-Casomorphin
  • β-Casomorphin analogs

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

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