RELATIVE EXPERIMENTAL CORONARY VASODILATOR POTENCIES AND TOXICITIES OF PAPAVERINE, THEOPHYLLINE, AND A PAPAVERINE-THEOPHYLLINE MOLECULAR ASSOCIATION COMPOUND

¹ Research Laboratories, Parke, Davis and Company, Detroit, Michigan

In the isolated rabbit heart, a molecular association compound of papaverine and theophylline was precisely equal in coronary-dilating potency to an equivalent equimolecular mixture of papaverine hydrochloride and theophylline. Papaverine hydrochloride was 18, +7 or -10 (95% confidence limits), times as potent as theophylline on a weight basis. On a molecular basis, theophylline was relatively so impotent that its contribution in the molecular association compound could not be detected, either on the coronary vascular bed, or in cardiovascular and respiratory effects in the anesthetized dog, by molecular comparison of the compound with papaverine hydrochloride. There was, indeed, a strong suggestion (P = ca. 0.05) that the presence of theophylline (competitively?) diminished papaverine's actions in the isolated heart.

However, at lethal dose levels (white mice), there was some suggestion (P = >0.05) that theophylline was beginning to contribute slightly to toxicity.