CORRELATION OF CHEMICAL STRUCTURE OF PHENO-THIAZINES WITH THEIR CORONARY DILATOR AND ANTIARRHYTHMIC ACTIVITIES

Courvoisier et al. (1) reported coronary vasodilator and antiarrhythmic activities of chlorpromazine. Arora (2) observed suppression of cardiac arrhythmias in dogs by tranquillisers including some phenothiazines. The coronary dilator activity of chlorpromazine was confirmed by Melville and Drapeu (3), and Kaverina (4) reported coronary dilator activity in several other phenothiazines. Chlorpromazine was found to be more potent than papaverine as coronary dilator (5) and it normalized the coronary blood flow in dogs following experimental myocardial infarction induced by ligation of coronary artery (6). Sharma and Arora (7) screened several phenothiazines for their antiarrhythmic activity in animals and found some of them superior to quinidine. Clinically also, chlorpromazine and a number of other phenothiazines have been successfully used in cases of coronary artery disease and cardiac arrhythmias (8, 9). Bhargava and Chandra (10, 11) reported the hypotensive, tranquillising and antiemetic activities of phenothiazines in relation to their chemical structure. Although isolated studies on the coronary dilator or antiarrhythmic activities of the phenothiazines are available, a combined study of the two properties in a series of phenothiazine compounds, in relation to their chemical structure, is lacking. The most common complication of coronary artery disease is cardiac arrhythmia, therefore, a phenothiazine derivative possessing coronary dilator activity coupled with antiarrhythmic property would be of immense therapeutic importance. Furthermore, the tranquillising property of such a compound would be an additional advantage. The present study was undertaken to evaluate a number of phenothiazines simultaneoulsy for these two activities and to make a possible correlation with their chemical structure.