Anti-inflammatory and antinociceptive effects of the selective cannabinoid CB2 receptor agonist ABK5

J Pharmacol Sci. 2021 Apr;145(4):319-326. doi: 10.1016/j.jphs.2020.12.006. Epub 2020 Dec 29.


Cannabinoid receptors are a potential target for anti-inflammatory and pain therapeutics. There are two subtypes, CB1 and CB2, and Δ9-tetrahydrocannabinol activates both of them, providing an analgesic effect but also psychoactive side effects. The psychoactive side effects are considered to be caused by activation of CB1, but not CB2. ABK5 is a CB2 subtype selective agonist that has a very different structure from known cannabinoid receptor agonists. Here, we report anti-inflammatory effects of ABK5 using the T-cell line Jurkat cells, and antinociceptive effect in an inflammatory pain model in rats. Production of the cytokines IL-2 and TNF-α was measured in stimulated Jurkat cells and MOLT-4 cells, and CXCL12-mediated chemotaxis of Jurkat cells was evaluated by a transwell migration assay. Anti-inflammatory and antinociceptive effects of ABK5 were also evaluated in a hindpaw CFA model in rats. ABK5 significantly decreased production of IL-2 and TNF-α measured as both mRNA and protein levels, and reduced chemotaxis towards CXCL12. It also attenuated edema and increased mechanical threshold in the hindpaw of CFA-treated rats. These results suggest that ABK5 is a good lead compound for the development of potential anti-inflammatory and analgesic agents.

Keywords: Anti-inflammation; Cannabinoid receptor CB(2) agonist; Cell migration; Inflammatory pain; Pro-inflammatory cytokines.

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Benzoates / pharmacology*
  • Chemokine CXCL12
  • Chemotaxis / drug effects
  • Disease Models, Animal
  • Female
  • Humans
  • Inflammation Mediators / metabolism
  • Interleukin-2 / metabolism
  • Jurkat Cells
  • Pain / drug therapy*
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB2 / agonists*
  • Sulfonamides / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism


  • Analgesics
  • Anti-Inflammatory Agents
  • Benzoates
  • CXCL12 protein, rat
  • Chemokine CXCL12
  • Inflammation Mediators
  • Interleukin-2
  • Receptor, Cannabinoid, CB2
  • Sulfonamides
  • Tumor Necrosis Factor-alpha
  • cannabinoid CB2 receptor agonist ABK5