Cyclothiazide (CTZ) is one of the most potent benzothiadiazides, a class of positive allosteric modulators of non-NMDA-type glutamate receptors that inhibit receptor desensitization with a marked selectivity for the flip splice variants of AMPA receptors. Specifically, CTZ is known to produce a fast inhibition of AMPA receptor desensitization and a much slower potentiation of the AMPA current. By using patch-clamp techniques, the effects of CTZ were studied in HEK 293 cells stably transfected with the rat flip GluR1 subunit. The AMPA currents were greatly potentiated by CTZ in a dose-dependent manner. For instance, pretreatment of the cells with 100 μM CTZ increased the peak AMPA currents by 90-fold (EC50 = 28 μM), the currents at the end of AMPA application by 636-fold (EC50 = 46 μM), and the current integrals by 730-fold (EC50 = 41 μM).
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