Diltiazem antiarrhythmic activity

Antiarrhythmic activity (verapamil, possibly also diltiazem) impairment of AV conduction and to a lesser degree also that of sinus node activity. 

The class IV-antiarrhythmics are the calcium antagonists, but remain limited to verapamil and possibly also diltiazem. The dihydropyridines (nifedipine and related compounds) are unsuitable for antiarrhythmic therapy. The antiarrhythmic activity of verapamil and diltiazem is based upon the impairment of AV conduction and heart rate. A few compounds may be considered to act as antiarrhyth-mics, but they are not included in the Vaughan-Williams classification. 

It is noteworthy that calcium inhibitory compounds with the ability to inhibit %a+ possess the most potent antiarrhythmic activity against both experimental and clinical arrhythmias (126). For example, nifedipine exerts minimal, if any, antiarrhythmic effect against ischemic induced arrhythmias in intact animals (6, 87, 131). Diltiazem and perhexiline, on the other hand, demonstrate variable antiarrhythmic effects dependent upon their dose and the mechanism responsible for arrhythmia production (ischemia, hypoxia, digitalis, aconitine) (102, 126, 151, 152). Only verapamil, which has been investigated in the largest number of experimental and clinical trials, has demonstrated consistent antiarrhythmic activity against cardiac arrhythmias regardless of cause (155) ... 

Berbamine was isolated from an extract of Berberis poiretii via bioassay-guided techniques using the 3H-diltiazem receptor binding assay. The alkaloid was found to possess calcium channel blocking activities (IC80 3 x 1CT6 M) and to act as an antiperoxidant as measured by the erythrocyte lipid peroxidation test. These data may provide information about the antimyocardial ischemic and antiarrhythmic effects of the berbamine [203]. 

Tamargo et al gave a very recent review.139 They point out that KATP channels are inhibited by ATP and activated by Mg ADP, so that the channel activity is influenced by the ATP/ADP ratio. They also draw attention to the fact that mitochondrial KATp channel is responsible for ischemic preconditioning. They suggest that these channels are not blocked only by sulfonylureas, but also by many antiarrhythmic drugs, such as bretylium, disopyramide, flecainide and propafenone, and also by diltiazem and verapamil, but not by amiodarone or dronedarone, which will be addressed later. 

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