Sotalol (3930-20-9) Mechanism Of Action
Sotalol powder is indicated to treat life threatening ventricular arrhytmias and maintain normal sinus rhythm in patients with atrial fibrillation or flutter.Label There are also oral solutions and intravenous injections indicated for patients requiring sotalol, but for whom a tablet would not be appropriate.
Sotalol powder is a competitive inhibitor of the rapid potassium
channel. This inhibition lengthens the duration of action potentials and
the refractory period in the atria and ventricles. The inhibition of
rapid potassium channels is increases as heart rate decreases, which is
why adverse effects like torsades de points is more likely to be seen at
lower heart rates.6 L-sotalol also has beta adrenergic receptor
blocking activity seen above plasma concentrations of 800ng/L. The beta
blocking ability of sotalol further prolongs action potentials.
D-sotalol does not have beta blocking activity but also reduces a
patient’s heart rate while standing or exercising. These actions combine
to produce a negative inotropic effect that reduces the strength of
contractility of muscle cells in the heart. Extension of the QT interval
is also adversely associated with the induction of arrhythmia in
patients.
Sotalol powder was first synthesized in 1960 by A. A. Larsen of
Mead-Johnson Pharmaceutical. It was originally recognized for its blood
pressure lowering effects and its ability to reduce the symptoms of
angina. It was made available in the United Kingdom and France in 1974,
Germany in 1975, and Sweden in 1979. It became widely used in the 1980s.
In the 1980s, its antiarrhythmic properties were discovered. The United
States approved the drug in 1992.
06 Sotalol (3930-20-9) Mechanism Of Action
Beta-blocker action
Sotalol non-selectively binds to both β1- and β2-adrenergic receptors preventing activation of the receptors by their stimulatory ligand (catecholamines). Without the binding of this ligand to the receptor, the G-protein complex associated with the receptor cannot activate production of cyclic AMP, which is responsible for turning on calcium inflow channels. A decrease in activation of calcium channels will therefore result in a decrease in intracellular calcium. In heart cells, calcium is important in generating electrical signals for heart muscle contraction, as well as generating force for this contraction. In consideration of these important properties of calcium, two conclusions can Beta-blocker action
Sotalol non-selectively binds to both β1- and β2-adrenergic receptors preventing activation of the receptors by their stimulatory ligand (catecholamines). Without the binding of this ligand to the receptor, the G-protein complex associated with the receptor cannot activate production of cyclic AMP, which is responsible for turning on calcium inflow channels. A decrease in activation of calcium channels will therefore result in a decrease in intracellular calcium. In heart cells, calcium is important in generating electrical signals for heart muscle contraction, as well as generating force for this contraction. In consideration of these important properties of calcium, two conclusions can be drawn. First, with less calcium in the cell, there is a decrease in electrical signals for contraction, thus allowing time for the heart’s natural pacemaker to rectify arrhythmic contractions. Secondly, lower calcium means a decrease in strength and rate of the contractions, which can be helpful in treatment of abnormally fast heart rates.
Type III antiarrhythmic action
Sotalol also acts on potassium channels and causes a delay in relaxation of the ventricles. By blocking these potassium channels, sotalol inhibits efflux of K+ ions, which results in an increase in the time before another electrical signal can be generated in ventricular myocytes. This increase in the period before a new signal for contraction is generated, helps to correct arrhythmias by reducing the potential for premature or abnormal contraction of the ventricles but also prolongs the frequency of ventricular contraction to help treat tachycardia.
