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Clemizole, also known as AL 20, P 48, or Reactrol, is a potent inhibitor of transient receptor potential channel TRPC5. Clemizole efficiently blocks TRPC5 currents and Ca(2+) entry in the low micromolar range (IC50 = 1.0-1.3 µM). Clemizole blocks TRPC5 currents irrespectively of the mode of activation. Based on fluorometric [Ca(2+)]i measurements, clemizole exhibits a sixfold selectivity for TRPC5 over TRPC4β (IC50 = 6.4 µM). Clemizole was not only effective in blocking heterologously expressed TRPC5 homomers but also TRPC1:TRPC5 heteromers as well as native TRPC5-like currents in the U-87 glioblastoma cell line.