Monoamine oxidase A inhibition by toxic concentrations of metaxalone

Brett Cherrington, Ulrich Englich, Supa Niruntari, William Grant, Michael Hodgman

Research output: Contribution to journalArticlepeer-review

Abstract

Context: Serotonin toxicity is a reported complication associated with both therapeutic use and overdose of metaxalone while on therapeutic doses of serotonergic drugs such as serotonin reuptake inhibitors. Monoamine oxidase A (MAO-A) inhibition by metaxalone has been proposed as the etiology of this toxicity. Metaxalone concentrations reported with cases of serotonin toxicity range from 31 to 61 mcg/ml (140–276 µM). We investigated the effect of metaxalone on MAO-A activity using an in vitro model. Methods: Metaxalone at concentrations ranging from 1.56 to 400 µM were incubated with a proprietary MAO substrate and recombinant human MAO-A for 1 h. After that, an esterase and luciferase were added and luminescence measured. Clorgyline, a known MAO-A inhibitor, was used as a positive control. Luminescence was measured using a Biotek Synergy HT microplate reader. Results: Metaxalone demonstrated significant dose-related inhibition of MAO-A activity. Four-parameter logistic regression analysis demonstrated a strong dose-response relationship at increasing concentrations. Conclusions: Our in vitro model shows that at toxic concentrations similar to those reported in case reports metaxalone shows significant MAO-A inhibition. Clinicians should be aware of this mechanism and understand the potentially lethal interactions metaxalone can have when prescribed with other serotonergic drugs and consider this as a potential cause of serotonin toxicity, especially in overdose scenarios.

Original languageEnglish (US)
Pages (from-to)383-387
Number of pages5
JournalClinical Toxicology
Volume58
Issue number5
DOIs
StatePublished - May 3 2020

Keywords

  • Metaxalone
  • monoamine oxidase A inhibition
  • overdose
  • serotonin toxicity

ASJC Scopus subject areas

  • Toxicology

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