Effect of Two Recently Synthesized Phenothiazine Derivatives Upon Experimental Cardiac Arrhythmias

Abstract

Chlorpromazine has been reported to suppress cardiac arrhythrnias produced ex perimentally (1, 2) and those observed in clinical practice (3). Two new phenothiazine derivatives, namely piperacetazine (2-acetyl-10-{-3 [-4-(fl-hydroxyethyl)-piper] dine] pro pyl}-phenothiazine) and benzosulfonate (1-methyl-2-{-(2-methylsulfinyl-dibenzothiazinyl 10)-ethyl-1 }-piperidine) have been recently synthesized (4, 5). Hence it is of interest to determine if they possess antiarrhythmic activity. MATERIAL AND METHODSFreshly prepared I % solutions in isotonic saline of benzosulfonate and piperacetazine were used. Cardiac arrhythmias were produced in vagotornized mongrel dogs of both sexes weighing between 8 and 18 kg by the following techniques:1. Acetylcholine-induced atrial fibrillation Twelve animals were anaesthetized with intravenous pentobarbital sodium, 30 mg/ kg. Atrial fibrillation was produced according to the method of Scherf and Chick (6) which was followed in all essential details as described by Schallek (7). A small pledget of cotton soaked in 5 per cent acetylcholine was placed on the area of sino-atrial node.One minute later, atrial fibrillation was induced by pinching the atrium and its duration noted. Two such controls were taken after which the procedure was repeated a third time. After the atria were fibrillating for a minute, the drug to be tested was injected and reduction in the duration of fibrillation noted. Atrial flutter incluced by injury-stimulationAccording to the method of Rosenblueth and Garcia Ramos (8) 3. Aconitine-induced atrial arrhythmia Atrial arrhythmia was produced by the method of Scherf (9) in 13 dogs which were anaesthetized as above. A cotton pledget soaked in 0.05% solution of aconitine hydro