Leucine enkephalin analogues containing a conformationally restrained N-terminal amino acid residue.

Three analogues of leucine enkephalin, in which the terminal tyrosine-1 residue has been replaced by conformationally restrained aromatic amino acids, have been synthesized by classical solution methods. Their opiate agonist potencies on electrically stimulated guinea pig ileum and mouse vas deferens preparations were determined and compared with morphine, Met enkephalin, and Leu enkephalin. None of these analogues had analgesic properties when evaluated on the above tissue preparations or when evaluated by the hot-plate test in mice after subcutaneous and intracerebroventricular administration.