B Spagnolo

Publications (3)10.12 Total impact

• Article: Activities of mixed NOP and μ‐opioid receptor ligands

  B Spagnolo, G Calo, W E Polgar, F Jiang, C M Olsen, I Berzetei-Gurske, T V Khroyan, S M Husbands, J W Lewis, L Toll, N T Zaveri
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  ABSTRACT: Background and purpose:Compounds that activate both NOP and μ-opioid receptors might be useful as analgesics and drug abuse medications. Studies were carried out to better understand the biological activity of such compounds.Experimental approach:Binding affinities were determined on membranes from cells transfected with NOP and opioid receptors. Functional activity was determined by [35S]GTPS binding on cell membranes and using the mouse vas deferens preparation in vitro and the tail flick antinociception assay in vivo.Key results:Compounds ranged in affinity from SR14150, 20-fold selective for NOP receptors, to buprenorphine, 50-fold selective for μ-opioid receptors. In the [35S]GTPS assay, SR compounds ranged from full agonist to antagonist at NOP receptors and most were partial agonists at μ-opioid receptors. Buprenorphine was a low efficacy partial agonist at μ-opioid receptors, but did not stimulate [35S]GTPS binding through NOP. In the mouse vas deferens, each compound, except for SR16430, inhibited electrically induced contractions. In each case, except for N/OFQ itself, the inhibition was due to μ-opioid receptor activation, as determined by equivalent results in NOP receptor knockout tissues. SR14150 showed antinociceptive activity in the tail flick test, which was reversed by the opioid antagonist naloxone.Conclusions and implications:Compounds that bind to both μ-opioid and NOP receptors have antinociceptive activity but the relative contribution of each receptor is unclear. These experiments help characterize compounds that bind to both receptors, to better understand the mechanism behind their biological activities, and identify new pharmacological tools to characterize NOP and opioid receptors.British Journal of Pharmacology (2008) 153, 609–619; doi:10.1038/sj.bjp.0707598; published online 3 December 2007
  British Journal of Pharmacology 01/2009; 153(3):609 - 619. · 4.41 Impact Factor
• Article: Activities of mixed NOP and mu-opioid receptor ligands.

  B Spagnolo, G Calo, W E Polgar, F Jiang, C M Olsen, I Berzetei-Gurske, T V Khroyan, S M Husbands, J W Lewis, L Toll, N T Zaveri
  [show abstract] [hide abstract]
  ABSTRACT: Compounds that activate both NOP and mu-opioid receptors might be useful as analgesics and drug abuse medications. Studies were carried out to better understand the biological activity of such compounds. Binding affinities were determined on membranes from cells transfected with NOP and opioid receptors. Functional activity was determined by [(35)S]GTPgammaS binding on cell membranes and using the mouse vas deferens preparation in vitro and the tail flick antinociception assay in vivo. Compounds ranged in affinity from SR14150, 20-fold selective for NOP receptors, to buprenorphine, 50-fold selective for mu-opioid receptors. In the [(35)S]GTPgammaS assay, SR compounds ranged from full agonist to antagonist at NOP receptors and most were partial agonists at mu-opioid receptors. Buprenorphine was a low efficacy partial agonist at mu-opioid receptors, but did not stimulate [(35)S]GTPgammaS binding through NOP. In the mouse vas deferens, each compound, except for SR16430, inhibited electrically induced contractions. In each case, except for N/OFQ itself, the inhibition was due to mu-opioid receptor activation, as determined by equivalent results in NOP receptor knockout tissues. SR14150 showed antinociceptive activity in the tail flick test, which was reversed by the opioid antagonist naloxone. Compounds that bind to both mu-opioid and NOP receptors have antinociceptive activity but the relative contribution of each receptor is unclear. These experiments help characterize compounds that bind to both receptors, to better understand the mechanism behind their biological activities, and identify new pharmacological tools to characterize NOP and opioid receptors.
  British Journal of Pharmacology 03/2008; 153(3):609-19. · 4.41 Impact Factor
• Article: Tryptophan replacement in the nociceptin/orphanin FQ receptor ligand Ac-RYYRWK-NH2.

  G Carra, G Calo, B Spagnolo, R Guerrini, M Arduin, E Marzola, C Trapella, D Regoli, S Salvadori
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  ABSTRACT: In the present study we describe the in vitro pharmacological characterization of the nociceptin/orphanin FQ (N/OFQ) receptor (NOP) ligand Ac-RYYRWK-NH2 and the synthesis and biological evaluation of 13 Trp5 substituted Ac-RYYRWK-NH2 analogs. Results indicate that Ac-RYYRWK-NH2 behaves as a highly potent and selective partial agonist at the NOP receptors and that the whole indole moiety of the Trp5 side chain is not required, being a phenyl-ethyl side chain already sufficient for maintaining high potency.
  European Journal of Allergy and Clinical Immunology 08/2005; 66(1):39-47. · 1.30 Impact Factor