A Novel Analgesic Isolated from a Traditional Chinese Medicine

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. [Display omitted] [Display omitted] •DHCB is isolated from C. yanhusuo, a plant used for centuries for pain relief•DHCB is antinociceptive against acute, inflammatory, and neuropathic pains•DHCB’s antinociception relies on its inhibitory activity at the dopamine D2 receptor•DHCB administration does not induce antinociceptive tolerance Zhang et al. apply reverse pharmacology on traditional Chinese medicines to identify dehydrocorybulbine (DHCB) as an analgesic alkaloid. DHCB exhibits antinociceptive effects against acute and chronic pains. DHCB’s antinociception relies on its inhibitory activity at the dopamine D2 receptor and does not induce tolerance.