title: Synthesis and opioid activity of [Sar4]dermorphin-tetrapeptide analogues.
abstract: The modification of the dermorphin-(1-4)-tetrapeptide structure led to analogues with potent opioid activity in vitro and in vivo. [Sar4]Tetrapeptides such as H2N-CH(NH)-Tyr-D-Ala-Phe-Sar-D-NH-CH(CH3)C6H5 (VII) whose terminal amino group is replaced by the guanidino function and whose C-terminus is amidated by (R)-(+)-alpha-methylbenzylamine, show peripheral and central opioid activities comparable to or higher than those of dermorphin. The potency of VII in the different tests was as follows: guinea-pig ileum (GPI) IC50 = 0.09nM, mouse Vas deferens (MVD) IC50 = 0.69nM, tail-flick ED50 = 8.91 pmol/mouse, i.c.v. and 4.54 mumol/kg, s.c. This dermorphin-(1-4)-tetrapeptide derivative is about 650 and 950 times as active as morphine in the two in vitro tests, respectively. The MVD/GPI potency ratio of the new peptides suggests a mu-type agonist behaviour.
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002855:Chromatography, Thin Layer / Q000379:methods; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009197:Myenteric Plexus / Q000187:drug effects; D009294:Narcotics / Q000138:chemical synthesis* / Q000494:pharmacology; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D018847:Opioid Peptides; D012521:Sarcosine / Q000494:pharmacology
chemical_list: D009294:Narcotics; D009842:Oligopeptides; D018847:Opioid Peptides; C030058:dermorphin; D012521:Sarcosine