title: Effectiveness of retigabine against levobupivacaine-induced central nervous system toxicity: a prospective, randomized animal study.
abstract: OBJECTIVE
  KCNQ2/3 channels play an important role in controlling neuronal excitability. Agents that decrease KCNQ2/3 current amplitudes are proconvulsant, whereas KCNQ2/3 current enhancers are anticonvulsant. Levobupivacaine is able to block the KCNQ2/3 channels and enhance neuronal excitation, whereas retigabine is able to reopen the channels and thus reduce overexcitation of neurons. In this study, we aimed to determine if retigabine is able to abolish local-anesthetic-induced seizures.
  
  
  METHODS
  Twenty New Zealand rabbits were randomly divided into two groups of ten. Levobupivacaine (0.5 %) was infused into conscious rabbits via the marginal ear vein at 8 ml/kg/h until the rabbits seized, and 5 mg/kg of retigabine were injected intravenously to terminate the seizure. The corresponding volume of saline was used as a control. The behavior of and the electroencephalogram (EEG) for each rabbit were continually monitored. Before levobupivacaine infusion, the rabbits were placed in a prostrate position calmly on the experimental platform, and the EEG pattern exhibited β waves. Intravenous levobupivacaine induced a typical EEG seizure characterized by multiple spike and slow wave complexes. The EEG changes were accompanied by behavioral convulsions which were characterized by clonic activity and opisthotonus.
  
  
  RESULTS
  Retigabine effectively terminated the electrographic and behavioral seizures. After receiving 5 mg/kg of retigabine, the animals became drowsy, and the EEG changed to δ waves.
  
  
  CONCLUSIONS
  We propose that KCNQ2/3 channels play an important role in levobupivacaine-induced central nervous system toxicity, and a KCNQ2/3 channel activator may be used to treat levobupivacaine-induced convulsions.
authors: Pain Medicine Center, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors: Yanxin
authors: Y
authors: Cheng
authors: Department of Anesthesiology, The Fourth Hospital of Shijiazhuang, Shijiazhuang, Hebei, China.
authors: Hong
authors: H
authors: Li
authors: Department of Anesthesiology, Kailuan General Hospital, Tangshan, Hebei, China.
authors: Jun
authors: J
authors: Li
authors: Department of Anesthesiology, Handan Center Hospital, Handan, Hebei, China.
authors: Yongxue
authors: Y
authors: Chen
authors: Pain Medicine Center, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
authors: Ran
authors: R
authors: Duan
authors: Department of Anesthesiology, Handan Center Hospital, Handan, Hebei, China.
authors: Jinge
authors: J
authors: Yuan
authors: Pain Medicine Center, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. senming63@163.com.
authors: Senming
authors: S
authors: Zhao
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002045:Bupivacaine / Q000031:analogs & derivatives* / Q000633:toxicity; D002219:Carbamates / Q000494:pharmacology*; D002490:Central Nervous System / Q000187:drug effects / Q000473:pathology; D051658:KCNQ2 Potassium Channel / Q000037:antagonists & inhibitors; D000077554:Levobupivacaine; D009474:Neurons / Q000187:drug effects; D010655:Phenylenediamines / Q000494:pharmacology*; D011446:Prospective Studies; D011817:Rabbits; D011897:Random Allocation; D012640:Seizures / Q000517:prevention & control*
chemical_list: D000927:Anticonvulsants; D002219:Carbamates; D051658:KCNQ2 Potassium Channel; D010655:Phenylenediamines; C101866:ezogabine; D000077554:Levobupivacaine; D002045:Bupivacaine
keywords: KCNQ2/3 channels; Local anesthetic toxicity; Retigabine; Seizure