Aim:To seek a novel and potent antitussive drug based on Shedan-Chuanbeipowder,a complex of traditional Chinese medicine preparation for cough therapy.Methods:Verticinone-cholic acid (Ver-CA) salt,a novel,salifying derivative ofverticinone and cholic acid,both of which are the major bioactive components inShedan-Chuanbei powder,was synthesized.We then evaluated the antitussiveactivity and the acute toxicity of the salt.Results:The new compound,with goodsolubility in water,has much more potent antitussive activity in comparison withthe same dose of single verticinone and single cholic acid.The administration 3mg/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 anti-tussive effect.On the other hand,glybenclamide (3 mg/kg,ip),an ATP-sensitiveK~+ 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 timesthat of verticinone.Conclusion:Based on the studies of pharmacology and acutetoxicity,the salt has a synergic and attenuated toxicity compared with singleverticinone and cholic acid.Moreover,the present study also suggests that Ver-CA,a potential novel antitussive agent,may exert its antitussive effect via boththe peripheral (modulated by ATP-sensitive K~+ channels) and central mechanisms(modulated by the opioid receptor). Aim: To seek a novel and potent antitussive drug based on Shedan-Chuanbeipowder, 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 inShedan-Chuanbei powder, was synthesized.We then evaluated the antitussiveactivity and the acute toxicity of the salt. Results: The new compound, with goodsolubility 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 more than 50% reduction of a citric acid-induced cough. Pretreatment with naloxone (0.8 mg / kg, ip) can only partially antagonize its anti -tussive effect.On the other hand, glybenclamide (3 mg / kg, ip), an ATP-sensitiveK ~ + channel blocker, also 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 timesthat of verticinone. Conflusion: Based on the studies of pharmacology and acute toxicity, the salt has a synergic and attenuated toxicity compared with singleverticinone and cholic acid. Moreover, the present study also suggests that Ver-CA, a potential novel antitussive agent, may exert its antitussive effect via both peripheral (modulated by ATP-sensitive K ~ + channels) and central mechanisms (modulated by the opioid receptor).