Double-enkephalins--synthesis, activity on guinea-pig ileum, and analgesic effect.
We have synthesized enkephalin analogues in which C-terminal methionine or leucine residues are replaced by a second active fragment of the enkephalin analogue. Synthesis of two compounds is described: in one, two fragments of a D-Ala2-enkephalin analogue are connected by a -NH-NH-bridge, and in the other, three methylene groups are incorporated between the amino groups. The first compound is a very potent inhibitor of electrically induced contractions of guinea-pig ileum and produces a strong analgesia when administered intraperitoneally in mice. The second compound is less active on the ileum and fails to produce analgesia after systemic injection. The double-enkephalins may interact with mu-receptors.
D000698:Analgesia; D000818:Animals; D001681:Biological Assay; D055598:Chemical Phenomena; D002621:Chemistry; D004744:Enkephalin, Methionine / Q000494:pharmacology; D004745:Enkephalins / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology
D004745:Enkephalins; D009270:Naloxone; D004744:Enkephalin, Methionine