Figure 18 Structure of the (a) cardioselective calcium channel blocker AH-1058, (b) the pacemaker current (If) blocker ivabradine and (c-g) RSD1235 and its congeners.
combination of IKur and IKACh blockade is exemplified by NIP-142 (49) which terminates atrial fibrillation and flutter in dogs, and has electrophysiological actions confined to atria. The rationale for IKACh block arises from the fact that ACh from cardiac parasympathetic nerves acts on atrial tissue to increase (hyperpolarize) the resting potential and reduce action potential duration, changes that induce arrhythmias. Thus, if IKACh is blocked, a source of arrhythmias is removed. ACh muscarinic blockers would accomplish the same end result in the heart, but they are not cardiac selective, and therefore produce unacceptable side effects.
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