Monoamine oxidase A inhibition by toxic concentrations of metaxalone

Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists
Brett CherringtonMichael Hodgman

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. Clinici...Continue Reading

References

Oct 24, 1998·Journal of Accident & Emergency Medicine·R J Daniels
Sep 13, 2003·British Journal of Clinical Pharmacology·Geoffrey K IsbisterAnthony J Smith
Nov 2, 2004·Journal of Analytical Toxicology·Justin L PoklisRuth E Winecker
Mar 8, 2005·Forensic Science International : Synergy·Karla A MooreDavid Fowler
Mar 24, 2005·The New England Journal of Medicine·Edward W Boyer, Michael Shannon
Nov 24, 2006·American Journal of Therapeutics·P ParuchuriS Niranjan
Nov 26, 2009·Human & Experimental Toxicology·Mathias B Forrester
Oct 25, 2011·Biomolecular Concepts·Helena Gaweska, Paul F Fitzpatrick
May 9, 2014·Journal of Medical Toxicology : Official Journal of the American College of Medical Toxicology·Adam R Bosak, Aaron B Skolnik
Feb 12, 2015·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Dyllon Ivy MartiniMichael Hodgman
Jan 1, 2012·International Journal of Medicinal Chemistry·Neha PanditBirendra Shrivastava
Jul 7, 2015·Journal of the American Podiatric Medical Association·Robert G FrykbergJaminelli Banks
Jul 15, 2015·The American Journal of Emergency Medicine·Ryan M SurmaitisMatthew D Cook
Sep 18, 2015·Journal of Analytical Toxicology·Sandra C Bishop-FreemanRuth E Winecker

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Citations

Aug 28, 2021·International Journal of Molecular Sciences·Giovanni PallioDomenica Altavilla

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