Differential signaling properties at the kappa opioid receptor of 12-epi-salvinorin A and its analogues.

Article Details

Citation

Copy to clipboard

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