MEDICINAL CHEMISTRY

influx through β-receptor blockade. Drugs in this class decrease neurologically induced
automaticity at normal therapeutic doses. At higher doses, these drugs may also exhibit
anesthetic properties, which cause decreased excitability, decreased conduction velocity,
and a prolonged effective refractory period. In normal therapeutic situations, the βblocking
effects are more important than any local anesthetic effects these drugs may
have. Propranolol is the prototype β-adrenergic blocker drug for class II.
β-Receptor antagonists exert their antiarrhythmic activity through their selective blockade
of β-receptors. They depress automaticity, prolong A.V. conduction, reduce heart rate,
and also decrease contractility. These drugs are primarily effective in treatment of
tachyarrhythmias caused by increased sympathetic activity.
Propranolol is primarily given orally for long-term treatment of cardiac arrhythmias. It
is useful in veiitricular arrhythmias that are due to enhanced adrenergic stimulation (from
emotional stress, exercise).
Acebutolol is a β1-selective adrenergic receptor blocker and is used chiefly for
controlling ventricular pressure beats. The principal metabolite is N-acetylacebutolol
(diacetolol) which is more potent and selective for β1-receptors than the parent drug.
Esmolol is particularly useful because of its very brief action (half-life 9 minutes) for the
treatment of supra ventricular tachycardias.
Sotalol is effective against both supraventricular and ventricular arrhythmias. It is a
much safer drug than amiodarone. It has a long half-life (about 15 hours).
Class III Antiarrhythmic Drugs
Class III drugs cause a homogeneous prolongation of the duration of the action potential.
This results in a prolongation of the effective refractory period. It is believed that most of
Class III antiarrhythmic agents act through phase 3 of the action potential by blocking
potassium channels.
Br
CH 3
+ -
CH2N CH2CH3 CH 3
SO 3
CH 3
Bretylium Tosylate (172)
Bretylium tosylate: N-(2-Bromobenzyl)-N-ethyl-N, N dimethyl ammonium p-toluene
sulfonate (172), chemically, bretylium belongs to the class of quaternary ammonium
compounds and simultaneously prolongs the action potential and the effective refractory
period. Bretylium is reserved for life-threatening ventricular arrhythmias that are
refractory to other therapy. Its use is confined to intensive care units. Oral absorption of
bretylium is poor. Its elimination half-time is approximately 6-10 hours.