title: Interaction among hERG channel blockers is a potential mechanism of death in caffeine overdose.
abstract: Caffeine overdose death is due to cardiac arrest, but its mechanism has not been explored in detail. In this study, our data showed that caffeine significantly prolonged the heart rate-corrected QT interval (QTc) of rabbits in vivo (P<0.05; n=7). Caffeine was also found to be a hERG channel blocker with an IC50of 5.04mM (n=5). Although these two findings likely link caffeine overdose death with hERG channel blockade, the amount of caffeine consumption needed to reach the IC50is very high. Further study demonstrated that addition another hERG blocker could lower the consumption of caffeine significantly, no matter whether two hERG blockers share the same binding sites. Our data does not rule out other possibility, however, it suggests that there is a potential causal relationship between caffeine overdose death with hERG channel and the interaction among these hERG blockers.
authors.affiliation: Cardiovascular Division, Jiaxing No.2 Hospital, 1518 Central Circle Road South, Jiaxing 314001, PR China.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Chinese Herb Medicine Division, The Nurturing Station for the State Key Laboratory of Subtropical Silviculture, Zhejiang Agriculture and Forestry University, 88 North Circle Road, Lin'an 311300, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Safety Pharmacology Division, Olivepharmasolutions Ltd, 333 Changhong Road, Wukang 313200, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Xu
authors.affiliation: Safety Pharmacology Division, Olivepharmasolutions Ltd, 333 Changhong Road, Wukang 313200, PR China.
authors.forename: Qingmao
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Pathophysiology department, Medical School, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Pathophysiology department, Medical School, Zhejiang University, Hangzhou 310058, PR China.
authors.forename: Yueliang
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Chinese Herb Medicine Division, The Nurturing Station for the State Key Laboratory of Subtropical Silviculture, Zhejiang Agriculture and Forestry University, 88 North Circle Road, Lin'an 311300, PR China.
authors.forename: Liping
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Cardiovascular Division, Jiaxing No.2 Hospital, 1518 Central Circle Road South, Jiaxing 314001, PR China. Electronic address: jiangliqin@medmail.com.cn.
authors.forename: Liqin
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Chinese Herb Medicine Division, The Nurturing Station for the State Key Laboratory of Subtropical Silviculture, Zhejiang Agriculture and Forestry University, 88 North Circle Road, Lin'an 311300, PR China. Electronic address: ychen@zafu.edu.cn.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D001665:Binding Sites; D002110:Caffeine / Q000378:metabolism / Q000494:pharmacology*; D003643:Death; D004305:Dose-Response Relationship, Drug; D062787:Drug Overdose / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D004357:Drug Synergism; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006323:Heart Arrest / Q000209:etiology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D026902:Potassium Channel Blockers / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D016171:Torsades de Pointes / Q000209:etiology
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; D026902:Potassium Channel Blockers; D002110:Caffeine
keywords: 17β-estradiol; Caffeine; Cardiac electrophysiology; Cardiac toxicity; hERG