High Concentrations of Tranexamic Acid Inhibit Ionotropic Glutamate Receptors

Author:

Lecker Irene1,Wang Dian-Shi1,Kaneshwaran Kirusanthy1,Mazer C. David1,Orser Beverley A.1

Affiliation:

1. From the Departments of Physiology (I.L., D.-S.W., K.K., C.D.M., B.A.O.) and Anesthesia (C.D.M., B.A.O.), University of Toronto; Department of Anesthesia, Keenan Research Centre for Biomedical Science and the Li Ka Shing Knowledge Institute, St. Michael’s Hospital (C.D.M.); and Department of Anesthesia, Sunnybrook Health Sciences Centre (B.A.O.), Toronto, Ontario, Canada.

Abstract

Abstract Background The antifibrinolytic drug tranexamic acid is structurally similar to the amino acid glycine and may cause seizures and myoclonus by acting as a competitive antagonist of glycine receptors. Glycine is an obligatory co-agonist of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptors. Thus, it is plausible that tranexamic acid inhibits NMDA receptors by acting as a competitive antagonist at the glycine binding site. The aim of this study was to determine whether tranexamic acid inhibits NMDA receptors, as well as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate subtypes of ionotropic glutamate receptors. Methods Tranexamic acid modulation of NMDA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate receptors was studied using whole cell voltage-clamp recordings of current from cultured mouse hippocampal neurons. Results Tranexamic acid rapidly and reversibly inhibited NMDA receptors (half maximal inhibitory concentration = 241 ± 45 mM, mean ± SD; 95% CI, 200 to 281; n = 5) and shifted the glycine concentration–response curve for NMDA-evoked current to the right. Tranexamic acid also inhibited α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (half maximal inhibitory concentration = 231 ± 91 mM; 95% CI, 148 to 314; n = 5 to 6) and kainate receptors (half maximal inhibitory concentration = 90 ± 24 mM; 95% CI, 68 to 112; n = 5). Conclusions Tranexamic acid inhibits NMDA receptors likely by reducing the binding of the co-agonist glycine and also inhibits α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate receptors. Receptor blockade occurs at high millimolar concentrations of tranexamic acid, similar to the concentrations that occur after topical application to peripheral tissues. Glutamate receptors in tissues including bone, heart, and nerves play various physiologic roles, and tranexamic acid inhibition of these receptors may contribute to adverse drug effects.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Anesthesiology and Pain Medicine

Reference53 articles.

1. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion.;Cochrane Database Syst Rev,2011

2. Topical application of tranexamic acid for the reduction of bleeding.;Cochrane Database Syst Rev,2013

3. Tranexamic acid for the treatment of heavy menstrual bleeding: Efficacy and safety.;Int J Womens Health,2012

4. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) study.;Arch Surg,2012

5. Tranexamic acid reduces blood transfusions in revision total hip arthroplasty.;J Arthroplasty,2016

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