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: 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-Fuster, Z David Luo, Xinmiao Liang, Olivier Civelli
• Journal: Current biology : CB (Curr Biol) Vol. 24 Issue 2 Pg. 117-123 (Jan 20 2014) ISSN: 1879-0445 [Electronic] England
• PMID: 24388848 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Alkaloids
• Analgesics
• Isoquinolines
• dehydrocorybulbine

Topics

• Alkaloids (chemistry, isolation & purification, pharmacology)
• Analgesics (chemistry, isolation & purification, pharmacology)
• Animals
• Corydalis (chemistry)
• HEK293 Cells
• Humans
• Inflammation (complications)
• Isoquinolines (chemistry, isolation & purification, pharmacology)
• Male
• Medicine, Chinese Traditional
• Mice
• Pain (drug therapy, etiology)