| Abstract | AIM: To seek a novel and potent antitussive drug based on Shedan-Chuanbei powder, a complex of traditional Chinese medicine preparation for cough therapy. METHODS: Verticinone-cholic acid (Ver-CA) salt, a novel, salifying derivative of verticinone and cholic acid, both of which are the major bioactive components in Shedan-Chuanbei powder, was synthesized. We then evaluated the antitussive activity and the acute toxicity of the salt. RESULTS: The new compound, with good solubility in water, has much more potent antitussive activity in comparison with the same dose of single verticinone and single cholic acid. The administration 3 mg/kg of Ver-CA could result in over 50% reduction of a citric acid-induced cough. Pretreatment with naloxone (0.8 mg/kg, ip) can only partially antagonize its antitussive effect. On the other hand, glybenclamide (3 mg/kg, ip), an ATP-sensitive K+ channel blocker, can also significantly reduce the antitussive effect of Ver-CA. A further acute toxicity study showed that the LD(50) values of Ver-CA were 3 times that of verticinone. CONCLUSION: Based on the studies of pharmacology and acute toxicity, the salt has a synergic and attenuated toxicity compared with single verticinone and cholic acid. Moreover, the present study also suggests that Ver-CA, a potential novel antitussive agent, may exert its antitussive effect via both the peripheral (modulated by ATP-sensitive K+ channels) and central mechanisms (modulated by the opioid receptor). |
| Authors | Fang-Zhou Xu, Chang Chen, Yong-Hui Zhang, Han-Li Ruan, Hui-Fang Pi, Pong Zhang, Ji-Zhou Wu
(Affiliation: Faculty of Pharmaceutical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.)
|
| Journal | Acta pharmacologica Sinica
(Acta Pharmacol Sin)
Vol. 28
Issue 10
Pg. 1591-6
(Oct 2007)
ISSN: 1671-4083 China |
| PMID | 17883945
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
