Tranexamic Acid, a Widely Used Antifibrinolytic Agent, Causes Convulsions by a γ-Aminobutyric AcidA Receptor Antagonistic Effect
- 1 April 2002
- journal article
- Published by American Society for Pharmacology & Experimental Therapeutics (ASPET) in Journal of Pharmacology and Experimental Therapeutics
- Vol. 301 (1), 168-173
- https://doi.org/10.1124/jpet.301.1.168
Abstract
Application of 4-(aminomethyl)cyclohexanecarboxylic acid (tranexamic acid; TAMCA) to the central nervous system (CNS) has been shown to result in hyperexcitability and convulsions. However, the mechanisms underlying this action are unknown. In the present study, we demonstrate that TAMCA binds to the γ-aminobutyric acid (GABA) binding site of GABAA receptors in membranes from rat cerebral cortex and does not interfere withN-methyl-d-aspartate receptors. Patch-clamp studies using human embryonic kidney cells transiently transfected with recombinant GABAA receptors composed of α1β2γ2 subunits showed that TAMCA did not activate these receptors but dose dependently blocked GABA-induced chloride ion flux with an IC50 of 7.1 ± 3.1 mM. Application of TAMCA to the lumbar spinal cord of rats resulted in dose-dependent hyperexcitability, which was completely blocked by coapplication of the GABAA receptor agonist muscimol. These results indicate that TAMCA may induce hyperexcitability by blocking GABA-driven inhibition of the CNS.Keywords
This publication has 19 references indexed in Scilit:
- Wound HealingAnnals of the New York Academy of Sciences, 2001
- Tryptamine derivatives as non-competitive N-methyl-d-aspartate receptor blockers: studies using [3H]MK-801 binding in rat hippocampal membranesNeuroscience Letters, 2000
- Characterization of spinal amino acid release and touch-evoked allodynia produced by spinal glycine or GABAA receptor antagonistNeuroscience, 1999
- Tranexamic AcidDrugs, 1999
- GABAA and GABAB receptor agonists, partial agonists, antagonists and modulators: design and therapeutic prospectsEuropean Journal of Pharmaceutical Sciences, 1997
- The effect of spinal GABA receptor agonists on tactile allodynia in a surgically-induced neuropathic pain model in the ratPain, 1997
- L-lysine is a barbiturate-like anticonvulsant and modulator of the benzodiazepine receptorNeurochemical Research, 1995
- Spinal neuronal pathology associated with continuous intrathecal infusion ofN-methyl-d-aspartate in the ratActa Neuropathologica, 1990
- Inhibition of intrathecally administered picrotoxin- and bicuculline-induced convulsions in mice by pipecolic acid or GABAEuropean Journal of Pharmacology, 1985
- The role of antifibrinolytic therapy in the preoperative management of recently ruptured intracranial aneurysmsSurgical Neurology, 1981