Preclinical pharmacology of celiprolol: a cardioselective beta-adrenergic antagonist and mild vasodilator. Celiprolol is a new antihypertensive agent that represents a new generation of beta-blockers. It combines cardioselective beta-adrenergic antagonism (beta 1) with a mild vasodilation via vasoselective beta-adrenergic agonism (beta 2). Results of animal studies show that celiprolol has beta 1-antagonist potency similar to that of propranolol and atenolol, and cardioselectivity slightly greater than that of atenolol. Celiprolol does not produce bronchoconstriction but has mild propranolol-resistant bronchodilatory properties in cats. The compound also relaxes vascular smooth muscle in a propranolol-sensitive fashion, suggesting a mechanism of beta 2-agonism. The beta 2-agonism results in a selective downregulation in beta 2-receptor number and response in tissue culture, as well as in peripheral tissue from celiprolol-treated volunteers. The decreases in beta 2-receptors are blocked by concomitant treatment with propranolol. Celiprolol is devoid of cardiac depressant activity and in fact has mild cardiostimulatory actions. The cardiostimulation is not via beta 1-stimulation, since it is not abolished by beta-blocking doses of propranolol. In a model of severe myocardial ischemia, celiprolol attenuates the ischemia-induced myocardial acidosis and improves the regional segment function. These results are suggestive of myocardial protection. In summary, celiprolol distinguishes itself from other beta-blockers by virtue of its cardioselectivity, vasorelaxation via beta 2-agonism, and the lack of bronchoconstriction and cardiodepression. These properties observed in animal studies have also been documented in clinical trials. 