Synthetic tetrapeptides related to dermorphin: potent long lasting analgesic action following subcutaneous administration.
To examine the opioid properties of D-MetO2-dermorphin tetrapeptides, eight new analogues based on the following formula, X-Tyr-D-MetO-Phe-aa-Y, were prepared. All these peptides show dose-related naloxone-reversible opioid effects in vitro and in vivo. Substitution of Sar or Gly-ol for Gly4 were well tolerated by the isolated guinea pig-ileum preparation as well as in the tail-flick test, while alkyl-amidation of the C-terminal proved detrimental. The central activity of H-Tyr-D-MetO-Phe-Gly-NH2, the most potent compound in the series, was higher than that of dermorphin. Following intracerebroventricular or subcutaneous administrations in mice, H-Tyr-D-MetO-Phe-Gly-NH2 was about 1500 and 17 times as analgesic as morphine, respectively.
D000595:Amino Acid Sequence; D000700:Analgesics; D000818:Animals; D001681:Biological Assay; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007279:Injections, Subcutaneous; D009842:Oligopeptides / Q000008:administration & dosage* / Q000138:chemical synthesis; D018847:Opioid Peptides; D013329:Structure-Activity Relationship
D000700:Analgesics; D009842:Oligopeptides; D018847:Opioid Peptides; C030058:dermorphin