Effects of a quaternary lidocaine derivative, QX-314, on the respiratory activity in brainstem-spinal cord preparation from newborn rats.

Kenichi Takahashi, Chikara Hayakawa, Hiroshi Onimaru

Neuroscience letters 2016 Apr 21

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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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Citation

Kenichi Takahashi, Chikara Hayakawa, Hiroshi Onimaru. Effects of a quaternary lidocaine derivative, QX-314, on the respiratory activity in brainstem-spinal cord preparation from newborn rats. Neuroscience letters. 2016 Apr 21;619:121-5