Anti-inflammatory and antinociceptive effects of the selective cannabinoid CB 2 receptor agonist ABK5

Yaliang Tang; Barbara Wolk; Stevie C Britch; Rebecca M Craft; Debra A Kendall

doi:10.1016/j.jphs.2020.12.006

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Anti-inflammatory and antinociceptive effects of the selective cannabinoid CB 2 receptor agonist ABK5

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Anti-inflammatory and antinociceptive effects of the selective cannabinoid CB 2 receptor agonist ABK5

Yaliang Tang, Barbara Wolk, Stevie C Britch, Rebecca M Craft and Debra A Kendall

Journal of pharmacological sciences, Vol.145(4), pp.319-326

04/2021

DOI: https://doi.org/10.1016/j.jphs.2020.12.006

PMID: 33712283

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Abstract

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

Cannabinoid receptors are a potential target for anti-inflammatory and pain therapeutics. There are two subtypes, CB and CB , and Δ -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 CB , but not CB . ABK5 is a CB 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.

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Title: Anti-inflammatory and antinociceptive effects of the selective cannabinoid CB 2 receptor agonist ABK5
Creators: Yaliang Tang - Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269, USA
Barbara Wolk - Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269, USA
Stevie C Britch - Department of Psychology, Washington State University, Pullman, WA, 99164, USA
Rebecca M Craft - Washington State University
Debra A Kendall - Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269, USA. Electronic address: debra.kendall@uconn.edu
Publication Details: Journal of pharmacological sciences, Vol.145(4), pp.319-326
Academic Unit: Psychology, Department of
Publisher: Japanese Pharmacological Soc
Number of pages: 8
Grant note: R21 DA040920 / NIDA NIH HHS
Identifiers: 99900907795901842
Language: English
Resource Type: Accepted manuscript