Characterization of a Cannabinoid CB2 Receptor-Selective Agonist, A-836339 [2,2,3,3-Tetramethyl-cyclopropanecarboxylic Acid [3-(2-Methoxy-ethyl)-4,5-dimethyl-3H-thiazol-(2Z)-ylidene]-amide], Using in Vitro Pharmacological Assays, in Vivo Pain Models, and Pharmacological Magnetic Resonance Imaging

@article{Yao2009CharacterizationOA,
  title={Characterization of a Cannabinoid CB2 Receptor-Selective Agonist, A-836339 [2,2,3,3-Tetramethyl-cyclopropanecarboxylic Acid [3-(2-Methoxy-ethyl)-4,5-dimethyl-3H-thiazol-(2Z)-ylidene]-amide], Using in Vitro Pharmacological Assays, in Vivo Pain Models, and Pharmacological Magnetic Resonance Imaging},
  author={Betty Bei Yao and Gin C. Hsieh and Anthony V. Daza and Yihong Fan and George K Grayson and Tiffany Runyan Garrison and Odile F El Kouhen and Bradley A. Hooker and Madhavi Pai and Erica J. Wensink and Anita K. Salyers and Prasant Chandran and Chang Z. Zhu and Chengmin Zhong and Keith B. Ryther and Megan E. Gallagher and Chih-Liang Chin and Ann Tovcimak and Vincent P. Hradil and Gerard B. Fox and Michael J. Dart and Prisca Honore and Michael D. Meyer},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  year={2009},
  volume={328},
  pages={141 - 151}
}
  • B. Yao, G. Hsieh, +20 authors M. Meyer
  • Published 2009
  • Chemistry, Medicine
  • Journal of Pharmacology and Experimental Therapeutics
Studies demonstrating the antihyperalgesic and antiallodynic effects of cannabinoid CB2 receptor activation have been largely derived from the use of receptor-selective ligands. Here, we report the identification of A-836339 [2,2,3,3-tetramethyl-cyclopropanecarboxylic acid [3-(2-methoxy-ethyl)-4,5-dimethyl-3H-thiazol-(2Z)-ylidene]-amide], a potent and selective CB2 agonist as characterized in in vitro pharmacological assays and in in vivo models of pain and central nervous system (CNS) behavior… Expand
Development of a High-Affinity PET Radioligand for Imaging Cannabinoid Subtype 2 Receptor.
TLDR
A library of fluorinated analogues aiming for an [(18)F]-labeled radiotracer with improved CB2 binding affinity and selectivity was designed and specific binding was shown in vitro, whereas fast metabolism was observed in vivo in CD-1 mice. Expand
Synthesis and biodistribution of [11C]A-836339, a new potential radioligand for PET imaging of cannabinoid type 2 receptors (CB2).
TLDR
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S-777469, a Novel Cannabinoid Type 2 Receptor Agonist, Suppresses Itch-Associated Scratching Behavior in Rodents through Inhibition of Itch Signal Transmission
TLDR
The results suggest that S-777469 produces its antipruritic effects by inhibiting itch signal transmission through CB2 agonism. Expand
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Functional Selectivity in CB2 Cannabinoid Receptor Signaling and Regulation: Implications for the Therapeutic Potential of CB2 Ligands
Receptor internalization increases the flexibility and scope of G protein-coupled receptor (GPCR) signaling. CB1 and CB2 cannabinoid receptors undergo internalization after sustained exposure toExpand
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TLDR
It is demonstrated here that [18F]2f is a promising novel tracer for imaging CB2R in vivo using PET, and further investigation in animal models of inflammation will follow. Expand
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TLDR
It is believed that selective CB2 agonism may afford a superior analgesic agent devoid of the centrally mediated CB1 effects, and high value putative therapeutics for treating pain and other disease states are represented. Expand
Cholesterol as a modulator of cannabinoid receptor CB2 signaling
TLDR
It is demonstrated that cholesterol increases basal activation levels of the receptor and alters the pharmacological categorization of these ligands, which may have implications for screening of drug candidates in a search of modulators of GPCR activity. Expand
CB1 Knockout Mice Unveil Sustained CB2-Mediated Antiallodynic Effects of the Mixed CB1/CB2 Agonist CP55,940 in a Mouse Model of Paclitaxel-Induced Neuropathic Pain
TLDR
The results using the mixed CB1/CB2 agonist CP55,940 document that CB1 and CB2 receptor activations produce mechanistically distinct suppression of neuropathic pain. Expand
2,3‐Dihydro‐1‐Benzofuran Derivatives as a Series of Potent Selective Cannabinoid Receptor 2 Agonists: Design, Synthesis, and Binding Mode Prediction through Ligand‐Steered Modeling
TLDR
A new series of 2,3‐dihydro‐1‐benzofuran derivatives bearing an asymmetric carbon atom that behave as potent selective CB2 agonists is designed and synthesized using a multidisciplinary medicinal chemistry approach with binding mode prediction through ligand‐steered modeling. Expand
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