Amiodarone: biochemical evidence for binding to a receptor for class I drugs associated with the rat cardiac sodium channel.

Amiodarone has multiple pharmacological effects in heart. Electrophysiological data suggest that among its other effects, amiodarone is a sodium channel blocker. Using a radioligand assay, we determined whether amiodarone interacted with a previously described receptor for type I agents associated with the cardiac sodium channel. The radioligand was [3H]batrachotoxinin A 20 alpha-benzoate ([ 3H]BTXB), a toxin that binds to the activated state of the sodium channel. We have previously shown that class I antiarrhythmic drugs inhibit [3H]BTXB binding. The purpose of this study was to assess whether amiodarone and other class III agents interact with this receptor. Amiodarone inhibited [3H]BTXB binding in a dose-dependent fashion, with an estimated IC50 value of 3.6 microM. This IC50 value is similar to reported clinically effective serum concentrations of amiodarone. In contrast to amiodarone, the IC50 values for other class III drugs (bretylium, sotalol, bethanidine, N-acetylprocainamide) were much higher t...