title: Effects of a quaternary lidocaine derivative, QX-314, on the respiratory activity in brainstem-spinal cord preparation from newborn rats.
abstract: In the clinical setting, the use of QX-314 (a quaternary derivative of lidocaine) has been proposed to achieve the selective inhibition of nociceptors that express transient receptor potential vanilloid 1 (TRPV1) channels with fewer motor deficits. However, it has been also reported that QX-314 may produce systemic CNS toxicities with relative potencies that are approximately twice as high as those of lidocaine. There are no reports concerning the effects of extracellular QX-314 on the rhythm-generating neurons in the respiratory center. In the present study, we examined the effects of QX-314 on respiratory rhythm generation in brainstem-spinal cord preparations from newborn rats. The extracellular application of QX-314 (200μM) decreased the C4 burst rate, amplitude and slope during the initial rising phase, and the effects slowly developed with a half-decay time of approximately 20min. The combined application of capsaicin (10 or 100μM) with QX-314 (100μM) showed no additional effect. The intracellular application of QX-314 (100μM) to respiratory neurons depressed the action potentials with a half-decay time of around 5min. Our findings could explain one of the mechanisms underlying the central toxicities that occur after the systemic application of QX-314.
authors.affiliation: Department of Physiology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan; Department of Anesthesiology, Showa University Northern Yokohama Hospital, 35-1 Chigasaki Chuou, Tsuzuki-ku, Yokohama-shi, Kanagawa 224-8503, Japan. Electronic address: hashikenkenken0717@gmail.com.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Orthopedic Surgery, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. Electronic address: chkra88kw@med.showa-u.ac.jp.
authors.forename: Chikara
authors.initials: C
authors.lastname: Hayakawa
authors.affiliation: Department of Physiology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. Electronic address: oni@med.showa-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Onimaru
mesh_terms: D000200:Action Potentials; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010507:Periodicity; D012125:Respiratory Center / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
chemical_list: D000779:Anesthetics, Local; C012647:QX-314; D008012:Lidocaine
keywords: Newborn rat; QX-314; Respiratory rhythm; in vitro