Synthesis, Opiate Receptor Binding and Analgesic Activity of Enkephalin Analogues

The synthesis and biological testing of analogues of Met‐enkephalin, a recently discovered opioid peptide from mammalian brain, are described. Testing involved determination of affinity constants for an opiate receptor site and of analgesic potency in the tail‐flick test in mouse. The effects on opioid activity of modifying various parts of the enkephalin molecule are discussed. Tyr‐D‐Ala‐Gly‐MePheMet (O)‐ol The ending ‐ol added to the symbol of an amino acid designates the aminoalcohol obtained by reduction of the α‐carboxyl group of the amino acid. (FK 33‐824), which was highly active in these tests, was subsequently selected for clinical testing. The use of two complementary models ‐ in vitro binding studies and in vivo test for analgesia ‐ for the assessment of biological activity in the evaluation of analogues is explained.