title: Salvinorin A analogues PR-37 and PR-38 attenuate compound 48/80-induced itch responses in mice.
abstract: OBJECTIVE
  The opioid system plays a crucial role in several physiological processes in the CNS and in the periphery. It has also been shown that selective opioid receptor agonists exert potent inhibitory action on pruritus and pain. In this study we examined whether two analogues of Salvinorin A, PR-37 and PR-38, exhibit antipruritic properties in mice.
  
  
  METHODS
  To examine the antiscratch effect of PR-37 and PR-38 we used a mouse model of compound 48/80-induced pruritus. In order to elucidate the mechanism of action of tested compounds, specific antagonists of opioid and cannabinoid receptors were used. The effect of PR-37 on the CNS was assessed by measuring motor parameters and exploratory behaviours in mice.
  
  
  RESULTS
  PR-37 and PR-38, jnjected s.c., significantly reduced the number of compound 48/80-induced scratching behaviours in mice in a dose- and time-dependent manner. PR-38 was also active when orally administered. The antiscratch activity of PR-37 was blocked by the selective κ opioid receptor antagonist, nor-binaltorphimine, and that of PR-38 by the selective μ opioid receptor antagonist, β-funaltrexamine.
  
  
  CONCLUSIONS
  In conclusion, a novel framework for the development of new antipruritic drugs derived from salvinorin A has been validated.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Salaga
authors.affiliation: Department of BioMolecular Sciences, Division of Pharmacognosy and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS, USA.
authors.forename: P R
authors.initials: PR
authors.lastname: Polepally
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Zielinska
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Marynowski
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Fabisiak
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: N
authors.initials: N
authors.lastname: Murawska
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Sobczak
authors.affiliation: Department of Molecular Cytogenetic, Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzebiec, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Sacharczuk
authors.affiliation: Platform of Behavioural Analysis (SCAC), Institute for Research and Innovation in Biomedicine (IRIB), Faculty of Medicine & Pharmacy, University of Rouen, Rouen Cedex, France.
authors.forename: J C
authors.initials: JC
authors.lastname: Do Rego
authors.affiliation: Department of Pharmacology, Division of Chemical Biology and Medicinal Chemistry, Medical School, NIMH Psychoactive Drug Screening Program, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Roth
authors.affiliation: Department of BioMolecular Sciences, Division of Pharmacognosy and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Zjawiony
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Fichna
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use; D000818:Animals; D045785:Diterpenes, Clerodane / Q000737:chemistry* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D009292:Narcotic Antagonists / Q000627:therapeutic use; D011537:Pruritus / Q000139:chemically induced* / Q000517:prevention & control*; D003189:p-Methoxy-N-methylphenethylamine / Q000633:toxicity*
chemical_list: C000590927:2-O-cinnamoylsalvinorin B; D000701:Analgesics, Opioid; D045785:Diterpenes, Clerodane; D009292:Narcotic Antagonists; D003189:p-Methoxy-N-methylphenethylamine; C090499:salvinorin A