A Novel Analgesic Isolated from a Traditional Chinese Medicine

• DOI: 10.1016/j.cub.2013.11.039
• Publication Date: 2014-01-02T21:03:06Z
• Authors: Yan Zhang; Chaoran Wang; Lien Wang; Gregory Scott Parks; Xiuli Zhang; Zhimou Guo; Yanxiong Ke; Kang-Wu Li; Mi Kyeong Kim; Benjamin Vo; Emiliana Borrelli; Guangbo Ge; Ling Yang; Zhiwei Wang; M. Julia Garcia-F...; Z. David Luo; Xinmiao Liang; Olivier Civelli
• Keywords: Male; 0301 basic medicine; Biomedical and clinical sciences; Pain; Neurodegenerative; Medical and Health Sciences; Substance Misuse; Mice; 03 medical and health sciences; Alkaloids; Complementary and Integrative Health; Psychology; Animals; Humans; Medicine, Chinese Traditional; Peripheral Neuropathy; Inflammation; Analgesics; Biomedical and Clinical Sciences; Agricultural and Biological Sciences(all); Biochemistry, Genetics and Molecular Biology(all); Pain Research; Psychology and Cognitive Sciences; Neurosciences; Chinese Traditional; Pharmacology and Pharmaceutical Sciences; Biological Sciences; Isoquinolines; 3. Good health; Biological sciences; HEK293 Cells; Corydalis; Neurological; Medicine; Chronic Pain; Drug Abuse (NIDA only); Developmental Biology

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.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.Our study casts DHCB as a different type of analgesic compound and as a promising lead in pain management.