title: The quaternary lidocaine derivative QX-314 produces long-lasting intravenous regional anesthesia in rats.
abstract: BACKGROUND
  The lidocaine derivative, QX-314, produces long-lasting regional anesthesia in various animal models. We designed this study to examine whether QX-314 could produce long-lasting intravenous regional anesthesia (IVRA) in a rat model.
  
  
  METHODS
  IVRA was performed on tail of rats. EC50 (median effective concentration) of QX-314 in IVRA was determined by up-and-down method. IVRA on tail of rats was evaluated by tail-flick and tail-clamping tests. For comparison between QX-314 and lidocaine, 60 Sprague-Dawley rats were randomly divided into 6 groups (n = 10/group), respectively receiving 0.5 ml of 0.5% lidocaine, 0.25% QX-314, 0.5% QX-314, 1.0% QX-314, 2.0% QX-314 and normal saline. To explore the role of TRPV1 channel in IVRA of QX-314, 20 rats were randomly divided into 2 groups (n = 10/group), respectively receiving 0.5 ml of 1% QX-314 and 1% QX-314+75 µg/ml capsazepine. Toxicities of QX-314 on central nervous system and cardiac system were measured in rats according to Racine's convulsive scale and by electrocardiogram, respectively.
  
  
  RESULTS
  QX-314 could produce long-lasting IVRA in a concentration-dependent manner. EC50 of QX-314 in rat tail IVRA was 0.15 ± 0.02%. At concentration of 0.5%, IVRA duration of QX-314 (2.5 ± 0.7 hour) was significantly longer than that of 0.5% lidocaine (0.3 ± 0.2 hour, P<0.001). TRPV1 channel antagonist (capsazepine) could significantly reduce the effect of QX-314. For evaluation of toxicities, QX-314 at doses of 5 or 10 mg/kg did not induce any serious complications. However, QX-314 at dose of 20 mg/kg (1% QX-314 0.5 ml for a rat weighing 250 g) induced death in 6/10 rats.
  
  
  CONCLUSIONS
  QX-314 could produce long-lasting IVRA in a concentration-dependent manner. This long-lasting IVRA was mediated by activation of TRPV1 channels. Evaluation of toxic complications of QX-314 confirmed that low but relevant doses of QX-314 did not result in any measurable toxicity.
authors.affiliation: Department of Anesthesiology and Laboratory of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology and Laboratory of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology and Laboratory of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology and Laboratory of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liang
authors.affiliation: Department of Anesthesiology and Laboratory of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.
authors.forename: Daqing
authors.initials: D
authors.lastname: Liao
authors.affiliation: Department of Anesthesiology and Laboratory of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology and Laboratory of Anesthesia & Critical Care Medicine, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China; Department of Anesthesiology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Chen
mesh_terms: D000765:Anesthesia, Conduction; D000771:Anesthesia, Intravenous; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002319:Cardiovascular System / Q000000981:diagnostic imaging / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects; D008012:Lidocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D018962:Phlebotomy; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D013623:Tail; D014463:Ultrasonography
chemical_list: D000779:Anesthetics, Local; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C012647:QX-314; D008012:Lidocaine