title: Preclinical pharmacology of celiprolol: a cardioselective beta-adrenergic antagonist and mild vasodilator.
abstract: 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.
authors.affiliation: Department of Cardiovascular Biology, Rhône-Poulenc Rorer Central Research, King of Prussia, PA 19406.
authors.forename: M H
authors.initials: MH
authors.lastname: Perrone
authors.forename: J A
authors.initials: JA
authors.lastname: Barrett
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001993:Bronchodilator Agents / Q000494:pharmacology; D017272:Celiprolol; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007511:Ischemia / Q000188:drug therapy; D011412:Propanolamines / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000319:Adrenergic beta-Antagonists; D001993:Bronchodilator Agents; D011412:Propanolamines; D014665:Vasodilator Agents; D017272:Celiprolol