Cicloprolol Hydrochloride

Cicloprolol is a new beta-blocking agent with high selectivity for beta 1 receptors and high intrinsic sympathomimetic activity. We studied the acute hemodynamic effects of cicloprolol in nine subjects with no evidence of left ventricular dysfunction who underwent cardiac catheterization for the evaluation of chest pain. All patients had normal coronary angiography and left ventriculography. Left ventricular pressure was determined throughout the cardiac cycle using a Millar 8Fr Minotip catheter; an echocardiogram, phonocardiogram, and ECG were simultaneously recorded to obtain left ventricular pressure-diameter loops. All the measurements were repeated before and after the intravenous administration of cicloprolol. Cicloprolol was administered at increasing doses of 0.05, 0.10, and 0.25 mg/kg until a cardiac output increase of at least 15% over basal values was achieved. A decrease of mean arterial pressure or cardiac output after cicloprolol was not observed in any patient. Cicloprolol administration significantly increased cardiac output (24%), stroke volume (22%), and peak positive dP/dt (25%); no significant changes in heart rate, systemic blood pressure, right atrial pressure, or pulmonary artery pressures were observed. No significant change in the echocardiographic parameters occurred. Among the indices of left ventricular diastolic function, the time constant of isovolumetric relaxation was significantly decreased (-43%) after cicloprolol; moreover, the left ventricular pressure-diameter loop in the protodiastolic phase was shifted to the left following cicloprolol infusion. This study confirms that in subjects with normal left ventricular function cicloprolol can improve resting left ventricular systolic function, and it shows that this action can also be attended by a more rapid isovolumetric relaxation, similar to what has been observed with other sympathomimetic amines.

The new β‐adrenoceptor partial agonist cicloprolol acts as a β‐agonist at normal levels and as a β‐antagonist at high levels of adrenergic discharge. Treatment with cicloprolol should protect the heart against excessive stimulation, while providing a baseline level of sympathetic drive. The clinical interest of such a profile is, however, not yet established in heart failure. Accordingly this study examined the safety of oral cicloprolol, a step necessary before undertaking efficacy comparison with other compounds recently proposed to treat heart failure. Twenty‐five patients were studied. Cicloprolol was given once a day for 2 weeks in a crossover double‐blind placebo‐controlled design. Follow‐ups were obtained at baseline and at the end of each period. At baseline all patients had clear evidence of heart failure. Cicloprolol did not affect resting heart rate and blood pressure, but it reduced significantly peak exercise heart rate and peak rate‐pressure product. The effect was especially significant in patients with sinus rhythm. The drug did not induce bradycardia or arrhythmias. Resting and exercise ejection rate were not affected. Cicloprolol improved the quality of life and the work capacity of 5 of 12 patients with congestive failure due to ischemic etiology. Side effects were few and similar with placebo and cicloprolol. Thus, short‐term administration of cicloprolol is safe in moderate heart failure.