Abbildung 2: CIBIS II - Cardiac Insufficiency Bisoprolol Study - Objectives
Bisoprolol proved to be the compound with the highest ß1-selectivity in all in vitro and in vivo studies and in all animal species investigated. One measure of ß1-selectivity is the ratio of the constants of inhibition (ci) for the ß1- and ß2-receptor. The constants of inhibition of the ß-blockers bisoprolol, atenolol, betaxolol and propranolol were determined in ligand-binding studies using rat parotid gland (mainly occupied by ß1-receptors) and rat reticulocytes (mainly occupied by ß2-receptors) in human plasma: using a non-specific radiolabelled ligand, the ß1- and ß2-receptors of the rat parotid gland and reticulocytes were completely occupied. This cell suspension was then mixed with the plasma of volunteers pretreated with different ß-blockers. The non-specific radioligand was now displaced from the receptor by addition of this serum enriched with ß-blockers. Constants of inhibition of a characteristic magnitude for each ß-blocker and receptor type could be determined from these tests; the smaller the ci-value, the higher the affinity of the ß-blocker for the receptor type concerned. The ratio of ci/ß1 to ci/ß2 was 1:75 for bisoprolol, 1:35 for atenolol and betaxolol, 1:20 for metoprolol, and 1.8:1 for propranolol. Bisoprolol therefore proved to be the ß-blocker with the highest ß1-selectivity in this model as well.