RB-64 explained

RB-64 is a semi-synthetic derivative of salvinorin A. It is an irreversible agonist, with a reactive thiocyanate group that forms a bond to the κ-opioid receptor (KOR), resulting in very high potency.^[1] It is functionally selective, activating G proteins more potently than β-arrestin-2.^[2] RB-64 has a bias factor of up to 96 and is analgesic with fewer of the side-effects associated with unbiased KOR agonists.^[3] The analgesia is long-lasting. Compared with unbiased agonists, RB-64 evokes considerably less receptor internalization.

See also

• Herkinorin
• Salvinorin B methoxymethyl ether
• Salvinorin A
• Nalfurafine

Notes and References

1. Yan F, Bikbulatov RV, Mocanu V, Dicheva N, Parker CE, Wetsel WC, Mosier PD, Westkaemper RB, Allen JA, Zjawiony JK, Roth BL . 6 . Structure-based design, synthesis, and biochemical and pharmacological characterization of novel salvinorin A analogues as active state probes of the kappa-opioid receptor . Biochemistry . 48 . 29 . 6898–6908 . July 2009 . 19555087 . 2752672 . 10.1021/bi900605n .
2. White KL, Scopton AP, Rives ML, Bikbulatov RV, Polepally PR, Brown PJ, Kenakin T, Javitch JA, Zjawiony JK, Roth BL . 6 . Identification of novel functionally selective κ-opioid receptor scaffolds . Molecular Pharmacology . 85 . 1 . 83–90 . January 2014 . 24113749 . 3868907 . 10.1124/mol.113.089649 .
3. White KL, Robinson JE, Zhu H, DiBerto JF, Polepally PR, Zjawiony JK, Nichols DE, Malanga CJ, Roth BL . 6 . The G protein-biased κ-opioid receptor agonist RB-64 is analgesic with a unique spectrum of activities in vivo . The Journal of Pharmacology and Experimental Therapeutics . 352 . 1 . 98–109 . January 2015 . 25320048 . 4279099 . 10.1124/jpet.114.216820 .