In vitro and in vivo pharmacological characterization of two novel selective cannabinoid CB2 receptor inverse agonists

Maria G. Cascio, Daniele Bolognini, Roger G Pertwee, Enza Palazzo, Federico Corelli, Serena Pasquini, Vincenzo Di Marzo, Sabatino Maione

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)


We have previously developed quinolone-3-carboxamides with the aim of obtaining new ligands for both cannabinoid receptors, CB1 and CB2. Our preliminary screening led to the identification of cannabinoid receptor ligands characterized by high affinity and, in some cases, also selectivity for CB2 receptors. Specifically, three compounds, 1,2 and 3 showed high affinity for CB2 as well as high selectivity over CB1 receptors. In addition, the activity shown by 1 against the formalin-induced nocifensive response in mice, reported in our previous paper, suggests that quinolone-3-carboxamides possess anti-nociceptive properties. In the present work, we have performed functional in vitro bioassays with the aim of investigating the functional activity in the [S-35]GTF gamma S binding assay of the other two compounds that, like 1, behave as CB2 selective ligands, and their potential analgesic actions in vivo. We found that both 2 and 3 behave in vitro as CB2 inverse agonists and are able to decrease nociceptive behaviour in the late phase of the formalin test only at the highest dose tested, although, at lower doses, they prevent the anti-nociceptive effects of a selective CB2 partial agonist in the formalin test. These results identify in 2 and 3 two novel, potent and selective CB2 antagonists/inverse agonists and confirm previous reports in the literature that, in addition to agonists at cannabinoid CB2 receptors, also inverse agonists/antagonists at these receptors show promise as anti-inflammatory agents. (C) 2009 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)349-354
Number of pages6
JournalPharmacological Research
Issue number4
Early online date2 Dec 2009
Publication statusPublished - Apr 2010


  • analgesics
  • animals
  • CHO cells
  • cricetinae
  • cricetulus
  • cyclohexanols
  • drug inverse agonism
  • formaldehyde
  • guanosine 5'-O-(3-thiotriphosphate)
  • mice
  • molecular structure
  • pain
  • quinolones
  • radioligand assay
  • receptor, cannabinoid, CB1
  • receptor, cannabinoid, CB2
  • structure-activity relationship


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