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.
