title: A novel analgesic isolated from a traditional Chinese medicine.
abstract: BACKGROUND
  Current pain management is limited, in particular, with regard to chronic pain. In an attempt to discover novel analgesics, we combined the approach developed to characterize traditional Chinese medicine (TCM), as part of the "herbalome" project, with the reverse pharmacology approach aimed at discovering new endogenous transmitters and hormones.
  
  
  RESULTS
  In a plant used for centuries for its analgesic properties, we identify a compound, dehydrocorybulbine (DHCB), that is effective at alleviating thermally induced acute pain. We synthesize DHCB and show that it displays moderate dopamine receptor antagonist activities. By using selective pharmacological compounds and dopamine receptor knockout (KO) mice, we show that DHCB antinociceptive effect is primarily due to its interaction with D2 receptors, at least at low doses. We further show that DHCB is effective against inflammatory pain and injury-induced neuropathic pain and furthermore causes no antinociceptive tolerance.
  
  
  CONCLUSIONS
  Our study casts DHCB as a different type of analgesic compound and as a promising lead in pain management.
authors.affiliation: Department of Pharmacology, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
authors.forename: Chaoran
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Lien
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Gregory Scott
authors.initials: GS
authors.lastname: Parks
authors.affiliation: Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
authors.forename: Zhimou
authors.initials: Z
authors.lastname: Guo
authors.affiliation: School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Yanxiong
authors.initials: Y
authors.lastname: Ke
authors.affiliation: Department of Anesthesiology and Perioperative Care, University of California, Irvine, CA 92697, USA.
authors.forename: Kang-Wu
authors.initials: KW
authors.lastname: Li
authors.affiliation: Department of Anesthesiology and Perioperative Care, University of California, Irvine, CA 92697, USA.
authors.forename: Mi Kyeong
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Perioperative Care, University of California, Irvine, CA 92697, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Vo
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Emiliana
authors.initials: E
authors.lastname: Borrelli
authors.affiliation: Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
authors.forename: Guangbo
authors.initials: G
authors.lastname: Ge
authors.affiliation: Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: M Julia
authors.initials: MJ
authors.lastname: Garcia-Fuster
authors.affiliation: Department of Anesthesiology and Perioperative Care, University of California, Irvine, CA 92697, USA.
authors.forename: Z David
authors.initials: ZD
authors.lastname: Luo
authors.affiliation: Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. Electronic address: liangxm@dicp.ac.cn.
authors.forename: Xinmiao
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Pharmacology, University of California, Irvine, Irvine, CA 92697, USA; Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, CA 92697, USA; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: ocivelli@uci.edu.
authors.forename: Olivier
authors.initials: O
authors.lastname: Civelli
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000700:Analgesics / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D031311:Corydalis / Q000737:chemistry*; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000150:complications; D007546:Isoquinolines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D010146:Pain / Q000188:drug therapy* / Q000209:etiology
chemical_list: D000470:Alkaloids; D000700:Analgesics; D007546:Isoquinolines; C000609474:dehydrocorybulbine