herkinorin herkinorin herkinorin is an opioid analgesic that is an analogue of the natural product salvinorin a. it was discovered in 2005 during structure-activity relationship studies into neoclerodane diterpenes, the family of chemical compounds of which salvinorin a is a member. herkinorinclinical dataatc codenonelegal statuslegal status legal/uncontrolled identifiers iupac name methyl (2s,4ar,6ar,7r,9s,10as,10br)-9-benzoyloxy-2-(furan-3-yl)-6a,10b-dimethyl-4,10-dioxo-2,4a,5,6,7,8,9,10a-octahydro-1h-benzoisochromene-7-carboxylate cas number862073-77-6 ypubchem cid11431898chemspider9606773 yunii5xn29vgr24chemblchembl363324 ycomptox dashboard (epa)dtxsid30235444 chemical and physical dataformulac28h30o8molar mass494.540 g·mol−13d model (jsmol)interactive image smiles o=c(oc)34(cc5c(=o)o(c1ccoc1)c5(4c(=o)(oc(=o)c2ccccc2)c3)c)c inchi inchi=1s/c28h30o8/c1-27-11-9-18-26(32)36-21(17-10-12-34-15-17)14-28(18,2)23(27)22(29)20(13-19(27)25(31)33-3)35-24(30)16-7-5-4-6-8-16/h4-8,10,12,15,18-21,23h,9,11,13-14h2,1-3h3/t18-,19-,20-,21-,23-,27-,28-/m0/s1 ykey:pydqmxrfuvdchc-xaghgkqisa-n y ny (what is this?) (verify) unlike salvinorin a, which is a selective κ-opioid receptor agonist with no significant μ-opioid receptor affinity, herkinorin is predominantly a μ-opioid receptor agonist. compared to salvinorin a, herkinorin has 47× lower affinity for κ-opioid receptors (ki ＝ 90 nm vs ki ＝ 1.9 nm), and at least 25× higher affinity for μ-opioid receptors (ki ＝ 12 nm vs ki > 1000 nm), where it acts as a full agonist (ic50 ＝ 0.5 μm, emax ＝ 130% vs damgo). herkinorin is a semi-synthetic compound, made from salvinorin b, which is most conveniently made from salvinorin a by deacetylation, since, while both salvinorin a and salvinorin b are found in the plant salvia divinorum, salvinorin a is present in larger quantities. a study in primates showed it to act peripherally as both a μ- and κ-opioid receptor agonist with a fast onset of action. the study did not find any evidence of central activity in primates and questions whether herkinorin's effects are due entirely to peripheral binding. unlike most μ-opioid receptor agonists, herkinorin does not promote the recruitment of β-arrestin 2 to the intracellular domain of the μ-opioid receptor, or induce receptor internalization. this means that herkinorin may not produce tolerance and dependence in the same way as other opioids, although some development of tolerance through other mechanisms has been observed, and some other analogues related to herkinorin can recruit β-arrestins.