The activity of a new antianginal
drug,
nonachlazine, synthetized in the Institute of Pharmacology, Academy of Medical Sciences of the USSR, has been demonstrated using model
myocardial ischemias on anesthetized dogs and conscious cats. Antianginal activity was evaluated by ECG, epicardial electrogram,
lactate level, and
lactate/
pyruvate ratio in the venous blood flowing from the ischemic myocardial area. The study of the cardiotropic effect of
nonachlazine provided the following findings: (1)
nonachlazine enhances ino- and chronotropic functions of the heart via stimulation of its
beta-adrenergic receptors; (2)
nonachlazine's positive chronotropic effect is substantially less marked than the inotropic one; (3)
nonachlazine decreases the intensity of chronotropic reactions of the heart induced by isopreterenol. Biochemical analysis showed that in addition to its activation of oxidative phosphorylation, the ability of
nonachlazine to stimulate glycogenolysis is also of importance in the development of its antianginal effect. This conclusion has been suggested by the following: (1) in acute
myocardial ischemia,
nonachlazine decreased
lactate level and increased
ATP level up to the norm; (2) at day 3 after
ligation of the coronary artery,
nonachlazine did not change
lactate content, increased
ATP and
NAD, and decreased NADH2; (3) in experiments on rabbit myocardial mitochondria in vivo and in vitro
nonachlazine was found to stimulate oxidative phosphorylation; (4)
nonachlazine was found capable of increasing the
norepinephrine level and of increasing
phosphorylase a activity and the rate of glycogenolysis.