Differential signaling properties at the kappa opioid receptor of 12-epi-salvinorin A and its analogues.
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Beguin C, Potuzak J, Xu W, Liu-Chen LY, Streicher JM, Groer CE, Bohn LM, Carlezon WA Jr, Cohen BM
Differential signaling properties at the kappa opioid receptor of 12-epi-salvinorin A and its analogues.
Bioorg Med Chem Lett. 2012 Jan 15;22(2):1023-6. doi: 10.1016/j.bmcl.2011.11.128. Epub 2011 Dec 7.
- PubMed ID
- 22204910 [ View in PubMed]
- Abstract
The kappa opioid receptor (KOPR) has been identified as a potential drug target to prevent or alter the course of mood, anxiety and addictive disorders or reduce response to stress. In a search for highly potent and selective KOPR partial agonists as pharmacological tools, we have modified 12-epi-salvinorin A, a compound which we have previously observed to be a KOPR partial agonist. Five analogues of 12-epi-salvinorin A were synthesized and their effects on G protein activation as well as beta-arrestin2 recruitment were evaluated. Only 12-epi-salvinorin A (1) partially activated signaling through G proteins, yet acted as a full agonist in the beta-arrestin 2 DiscoveRx assay. Other salvinorin analogues tested in these functional assays were full agonists in both assays of KOPR activation. By comparison, the non-selective opioid ligand nalbuphine, known to be a partial agonist for G-protein activation, was also a partial agonist for the beta-arrestin mediated signaling pathway activated through KOPR.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Nalbuphine Kappa-type opioid receptor EC 50 (nM) 65 N/A N/A Details Nalbuphine Kappa-type opioid receptor EC 50 (nM) 250 N/A N/A Details