Antiarrhythmic drugs, clofilium and cibenzoline are potent inhibitors of glibenclamide‐sensitive K+ currents in Xenopus oocytes

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Abstract
The novel K+ channel opener, Y‐26763 induced outward K+ currents in voltage‐clamped follicle‐enclosed Xenopus oocytes in a concentration‐dependent manner with an EC50 value of 58 μm. The Y‐26763‐induced K+ current was completely and reversibly blocked by glibenclamide (an ATP‐sensitive K+ channel blocker) in a concentration‐dependent manner (IC50 140 nm). Effects of several antiarrhythmic drugs on Y‐26763‐induced glibenclamide‐sensitive K+ currents were investigated. (±)‐Cibenzoline, RS‐2135, pirmenol, lorcainide and KW‐3407 (class I antiarrhythmic drugs, Na+ channel blockers) suppressed Y‐26763 responses in a concentration‐dependent manner with IC50 values (in μm) of 6.6, 54, 68, 71 and 370, respectively. Clofilium, E‐4031, MS‐551 and bretylium (class III antiarrhythmic drugs which increase the action potential duration) also suppressed Y‐26763 responses concentration‐dependently, IC50 values (in μm) were 3.3, 660, 980 and ≥ 2000, respectively. N‐acetylprocainamide (class III antiarrhythmic drug) scarcely suppressed Y‐26763 responses. The glibenclamide‐sensitive K+ currents elicted by KRN2391 were also suppressed by all these antiarrhythmic drugs. The antiarrhythmic drugs, clofilium and (±)‐cibenzoline block glibenclamide‐sensitive K+ channels in Xenopus oocytes at concentrations comparable to their therapeutic plasma levels.