Cardiac electrophysiological effects of two class III antiarrhythmic agents, tedisamil and D-sotalol, evaluated in isolated guinea pig hearts

D-sotalol has emerged as the prototype of the so-called class III antiarrhythmic compounds. Its cardiac electro-physiological effects are described as a prolongation of the repolarization period by inhibition of the delayed rectifier potassium current . This property of prolonging the action potential duration, with an accompanying increase in the effective refractory period (ERP), is not due to a blockade of beta-adrenergic receptors because D-sotalol has only 2% of the beta-blocking activity of L-sotalol . D-sotalol further reduced the spontaneous sinus rate, which could be explained by a prolongation of the action potential of sinus node pacemaker cells . This is supported by the observation that the dextroisomer of the drug, which nearly lacks beta-blocking properties, induced the same effect on the repolarization period of the sinus node cells as the levoisomer.
Tedisamil (3,7-di-(cyclopropylmethyl)-9,9-tetramethyl-ene-3,7-diazabicyclo[3.3.1]nonane dihydrochloride) is a newly developed bradycardic and anti-ischemic agent. It has been described to reduce spontaneous pacemaker rate by prolongation of the repolarization period, while leaving pacemaker currents unaffected . Tedisamil further induced in in vitro and in vivo experiments, a marked prolongation of the repolarization period without major influence on the QRS duration . In patch and voltage clamp studies in rat ventricular myocytes, tedisamil suppressed two potassium currents: the transient outward potassium current and the delayed rectifier potassium current . In 20-fold higher doses it further blocked the sodium currents, while no effect on the calcium currents have been measured. Find best deals online – Asthma Inhalers Online only here can be available every time you visit.

Category: Cardiology

Tags: Conduction, D-sotalol, Guinea pig, Refractoriness, Repolarization, Tedisamil

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