Dextromethorphan inhibition of voltage-gated proton currents in BV2 microglial cells

Jin Ho Song*, Jay Z. Yeh

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Dextromethorphan, an antitussive drug, has a neuroprotective property as evidenced by its inhibition of microglial production of pro-inflammatory cytokines and reactive oxygen species. The microglial activation requires NADPH oxidase activity, which is sustained by voltage-gated proton channels in microglia as they dissipate an intracellular acid buildup. In the present study, we examined the effect of dextromethorphan on proton currents in microglial BV2 cells. Dextromethorphan reversibly inhibited proton currents with an IC 50 value of 51.7μM at an intracellular/extracellular pH gradient of 5.5/7.3. Dextromethorphan did not change the reversal potential or the voltage dependence of the gating. Dextrorphan and 3-hydroxymorphinan, major metabolites of dextromethorphan, and dextromethorphan methiodide were ineffective in inhibiting proton currents. The results indicate that dextromethorphan inhibition of proton currents would suppress NADPH oxidase activity and, eventually, microglial activation.

Original languageEnglish (US)
Pages (from-to)94-98
Number of pages5
JournalNeuroscience Letters
Issue number1
StatePublished - May 10 2012


  • 3-Hydroxymorphinan
  • Dextromethorphan
  • Dextrorphan
  • Microglial BV2 cell
  • Voltage-gated proton channel

ASJC Scopus subject areas

  • Neuroscience(all)


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