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As the membrane depolarizes, the Mg+2 block is removed (Nowak et al., 1984)

This led to the greater potency of KDS12017 (EC 50 = 0.09 M) and KDS12025 (EC 50 = 0.04 M), the latter being ~4-fold more potent than HTPEB (EC 50 = 0.15 M) (Fig