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 GABA_A 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 GABA_A 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 GABA_A receptor agonist muscimol. These results indicate that TAMCA may induce hyperexcitability by blocking GABA-driven inhibition of the CNS.