RT Journal Article
SR Electronic
T1 Tranexamic Acid, a Widely Used Antifibrinolytic Agent, Causes Convulsions by a γ-Aminobutyric Acid<sub>A</sub> Receptor Antagonistic Effect
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 168
OP 173
DO 10.1124/jpet.301.1.168
VO 301
IS 1
A1 Roman Furtmüller
A1 Michael G. Schlag
A1 Michael Berger
A1 Rudolf Hopf
A1 Sigismund Huck
A1 Werner Sieghart
A1 Heinz Redl
YR 2002
UL http://jpet.aspetjournals.org/content/301/1/168.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics