title: Antinociceptive effect of D-Lys(2), Dab(4)N-(ureidoethyl)amide, a new cyclic 1-4 dermorphin/deltorphin analog.
abstract: BACKGROUND
  A preliminary evaluation of antinociceptive activity of a new cyclic dermorphin/deltorphin tetrapeptide analog restricted via a urea bridge and containing C-terminal ureidoethylamid {[H-Tyr-d-Lys(&(1))-Phe-Dab(&(2))-CH2CH2NHCONH2][&(1)CO&(2)]} (cUP-1) revealed a significant and long-lasting increase of pain threshold to thermal stimulation after systemic application. The current studies were aimed at further evaluation of cUP-1 activity in animal models of somatic and visceral pain. The influence of cUP-1 on motor functions was also investigated.
  
  
  METHODS
  The influence of cUP-1 (0.5-2mgkg(-1), iv) on nociceptive threshold to mechanical pressure and analgesic efficacy in formalin and acetic acid-induced writhing tests were estimated. The antinociceptive effect of cUP-1 was compared to that of morphine (MF). The influence of cUP-1 (1, 4 and 8mgkg(-1), iv) on locomotor activity, motor coordination and muscle strength was estimated using open field and rota-rod tests and a grip strength measurement.
  
  
  RESULTS
  Administration of cUP-1 in doses of 1 and 2mgkg(-1) elicited a significant increase of nociceptive threshold to mechanical pressure. MF applied in the same doses induced an antinociceptive effect only at the higher dose (2mgkg(-1)). There were no marked differences between the effect of cUP-1 and MF at each dose, at relative time points. In the writhing test and both phases of the formalin test, cUP-1 showed a significant, dose-dependent antinociceptive effect which did not markedly differ from that of MF. cUP-1 did not significantly affect motor functions of mice.
  
  
  CONCLUSIONS
  Systemic application of cUP-1 elicited a dose-dependent antinociceptive effect. The analgesic efficacy of cUP-1 on mechanical nociception, visceral and formalin-induced pain was comparable to that of MF. cUP-1 did not impair motor functions of mice.
authors.affiliation: Military Institute of Hygiene and Epidemiology, Department of Pharmacology and Toxicology, Warsaw, Poland. Electronic address: bantkowiak@wihe.waw.pl.
authors.forename: Bożena
authors.initials: B
authors.lastname: Antkowiak
authors.affiliation: Military Institute of Hygiene and Epidemiology, Department of Pharmacology and Toxicology, Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Paluch
authors.affiliation: Military Institute of Hygiene and Epidemiology, Department of Pharmacology and Toxicology, Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Ciechanowska
authors.affiliation: Military Institute of Hygiene and Epidemiology, Department of Pharmacology and Toxicology, Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Nawrocka
authors.affiliation: Pharmaceutical Research Institute, Warsaw, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Bańkowski
authors.affiliation: Pharmaceutical Research Institute, Warsaw, Poland.
authors.forename: Olga
authors.initials: O
authors.lastname: Michalak
authors.affiliation: Military Institute of Hygiene and Epidemiology, Department of Pharmacology and Toxicology, Warsaw, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Kocik
authors.affiliation: Military Institute of Hygiene and Epidemiology, Department of Pharmacology and Toxicology, Warsaw, Poland; Józef Piłsudski University of Physical Education, Warsaw, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Kowalczyk
authors.affiliation: Warsaw University, Department of Chemistry, Warsaw, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Izdebski
mesh_terms: D000701:Analgesics, Opioid / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D008297:Male; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000187:drug effects; D059226:Nociceptive Pain / Q000188:drug therapy*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D045442:Rotarod Performance Test; D059265:Visceral Pain / Q000188:drug therapy
chemical_list: D000701:Analgesics, Opioid; D009842:Oligopeptides; D010456:Peptides, Cyclic; C000595049:cUP-1 peptide; C059567:deltorphin; C053416:tyrosyl-alanyl-phenylalanyl-glycine
keywords: Antinociception; Deltorphins; Dermorphin; Opioid peptide; Ureidopeptide