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Monoamine oxidase A inhibition by toxic concentrations of metaxalone

Brett Cherrington1,2, Ulrich Englich3, Supa Niruntari1,2

  • 1Upstate New York Poison Center, Syracuse, NY, USA.

Clinical Toxicology (Philadelphia, Pa.)
|August 3, 2019
PubMed

Insights

Metaxalone significantly inhibits monoamine oxidase A (MAO-A) activity in vitro at toxic concentrations. This finding suggests MAO-A inhibition as a potential cause of serotonin toxicity when metaxalone is combined with serotonergic drugs.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Toxicology

Background:

  • Serotonin toxicity is a known complication of metaxalone, particularly when co-administered with serotonergic drugs like SSRIs.
  • Metaxalone's potential inhibition of monoamine oxidase A (MAO-A) has been hypothesized as the underlying mechanism for this toxicity.
  • Reported metaxalone concentrations in toxicity cases range from 140-276 µM.

Purpose of the Study:

  • To investigate the in vitro effect of metaxalone on the activity of monoamine oxidase A (MAO-A).
  • To determine if metaxalone exhibits dose-dependent inhibition of MAO-A activity.

Main Methods:

  • Recombinant human MAO-A was incubated with varying concentrations of metaxalone (1.56–400 µM) for 1 hour.
  • MAO-A activity was assessed by measuring luminescence after the addition of a substrate, esterase, and luciferase.
  • Clorgyline, a known MAO-A inhibitor, served as the positive control.

Main Results:

  • Metaxalone demonstrated significant, dose-related inhibition of MAO-A activity across the tested concentrations.
  • Four-parameter logistic regression analysis confirmed a strong dose-response relationship between metaxalone concentration and MAO-A inhibition.
  • The observed inhibition occurred at concentrations comparable to those reported in clinical cases of metaxalone-associated serotonin toxicity.

Conclusions:

  • This in vitro study confirms that metaxalone significantly inhibits MAO-A activity at toxic concentrations.
  • Clinicians should consider MAO-A inhibition by metaxalone as a potential cause of serotonin toxicity, especially in overdose or when combined with other serotonergic agents.
  • Awareness of this pharmacodynamic interaction is crucial for managing patients on metaxalone and serotonergic medications.
Keywords:
Metaxalonemonoamine oxidase A inhibitionoverdoseserotonin toxicity

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