|
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.〔() Harding WW, Tidgewell K, Byrd N, Cobb H, Dersch CM, Butelman ER, Rothman RB, Prisinzano TE. "Neoclerodane diterpenes as a novel scaffold for mu opioid receptor ligands." ''Journal of Medicinal Chemistry''. 2005 Jul 28;48(15):4765-71. PMID 16033256〕 Unlike Salvinorin A which is a selective κ-opioid agonist with no significant μ-opioid receptor affinity, herkinorin is a μ-opioid agonist with more than 100x higher μ-opioid affinity and 50x lower κ-opioid affinity compared to Salvinorin A.〔() Tidgewell K, Harding WW, Lozama A, Cobb H, Shah K, Kannan P, Dersch CM, Parrish D, Deschamps JR, Rothman RB, Prisinzano TE. "Synthesis of salvinorin A analogues as opioid receptor probes." ''Journal of Natural Products''. 2006 Jun;69(6):914-8. PMID 16792410〕〔() Holden KG, Tidgewell K, Marquam A, Rothman RB, Navarro H, Prisinzano TE. Synthetic studies of neoclerodane diterpenes from Salvia divinorum: Exploration of the 1-position. ''Bioorganic and Medicinal Chemistry Letters''. 2007 Nov 15;17(22):6111-5. PMID 17904842〕 Herkinorin is a semi-synthetic compound, made from Salvinorin B, which is most conveniently made from Salvinorin A by deacetylation, as while both Salvinorin A and Salvinorin B are found in the plant ''Salvia divinorum'', Salvinorin A is present in larger quantities.〔() Tidgewell K, Harding WW, Schmidt M, Holden KG, Murry DJ, Prisinzano TE. "A facile method for the preparation of deuterium labeled salvinorin A: synthesis of ()-salvinorin A." ''Bioorganic and Medicinal Chemistry Letters''. 2004; 14: 5099-5102. PMID 15380207〕 A study in primates showed it to act as both a peripherally active μ and κ 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 agonists, herkinorin does not promote the recruitment of β-arrestin-2 to the intracellular domain of the μ-opioid receptor, or induce receptor internalization.〔() Groer CE, Tidgewell K, Moyer RA, Harding WW, Rothman RB, Prisinzano TE, Bohn LM. "An opioid agonist that does not induce μ-opioid receptor--arrestin interactions or receptor internalization." ''Molecular Pharmacology''. 2007 Feb;71(2):549-57. PMID 17090705〕 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,〔() Xu H, Partilla JS, Wang X, Rutherford JM, Tidgewell K, Prisinzano TE, Bohn LM, Rothman RB. "A comparison of noninternalizing (herkinorin) and internalizing (DAMGO) mu-opioid agonists on cellular markers related to opioid tolerance and dependence." ''Synapse''. 2007 Mar;61(3):166-75. PMID 17152090〕 and some other analogues related to herkinorin can recruit β-arrestins. == See also == * 2-Ethoxymethyl Salvinorin B * 2-Methoxymethyl Salvinorin B * RB-64 * Salvinorin A 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Herkinorin」の詳細全文を読む スポンサード リンク
|