O Cardioselective Ca2 + channel blocker AH-1058

Unfortunately, the prototypical antiarrhythmic L-type Ca2 + channel blocker, verapamil (28), is not selective for cardiac versus vascular tissue. Early work suggested that if a calcium channel blocker had selective actions in ischemic cardiac tissue, it would be selective in its actions against ischemia-induced ventricular arrhythmias. There have been few efforts to follow this path although a new cyproheptadine derivative, AH-1058 (50), was developed to block L-type Ca2 + channels with better cardiac selectivity and limited vasodilator actions. AH-1058 (Figure 18) suppresses ventricular arrhythmias in dogs, but its negative effects on cardiac contractions coupled with limited hypotension may limit its utility in patients with cardiac contractile dysfunction, as in heart failure.28

The class 5 designation was created for specific bradycardic drugs that slowed the SA node rate. Alinidine (30) (Figure 12) was the prototype for such compounds with newer ones including the novel pacemaker current (If) inhibitor ivabradine (51) which blocks If at high potency.10 It is an open-channel blocker with a favorable 'positive use-dependence' that should potentially make ivabradine more effective in reducing heart rate during SA node tachycardia.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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