文献类型：期刊文献

英文题名：A Novel Analgesic Isolated from a Traditional Chinese Medicine

作者：Zhang, Yan[1];Wang, Chaoran[2];Wang, Lien[1];Parks, Gregory Scott[1];Zhang, Xiuli[2];Guo, Zhimou[2];Ke, Yanxiong[3];Li, Kang-Wu[4];Kim, Mi Kyeong[4];Vo, Benjamin[4];Borrelli, Emiliana[5];Ge, Guangbo[2];Yang, Ling[2];Wang, Zhiwei[1];Garcia-Fuster, M. Julia[1];Luo, Z. David[4];Liang, Xinmiao[2,3];Civelli, Olivier[1,6,7]

机构：[1]Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92697 USA;[2]Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, Peoples R China;[3]E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China;[4]Univ Calif Irvine, Dept Anesthesiol & Perioperat Care, Irvine, CA 92697 USA;[5]Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA;[6]Univ Calif Irvine, Dept Pharmaceut Sci, Irvine, CA 92697 USA;[7]Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA

年份：2014

卷号：24

期号：2

起止页码：117

外文期刊名：CURRENT BIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000329944400017)】；

基金：We would like to thank Richard Chamberlin, James D. Belluzzi, Jim Carolan, and Amal Alachkar for helpful discussions and Lily Tamura for proof reading. This work was supported by National Institutes of Health grants MH60231 and DA024746, an Established Investigator Award from the National Alliance for Research on Schizophrenia and Depression (NARSAD), and a Tourette Syndrome Association award to O.C. This work was also supported by the Key Program of National Natural Science Foundation of China (grant number 21135005) and the Major Project of National High Technology Research and Development Program of China (863 Program, 2012AA020203).

语种：英文

摘要：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.