title: The effects of (+/-)-, (+)- and (-)-celiprolol and bromoacetylalprenololmentane at the beta-adrenoceptors of rat isolated cardiovascular preparations.
abstract: The effects of (+/-)-, (+)- and (-)-celiprolol and of bromoacetylalprenololmentane (BAAM, an irreversible beta-adrenoceptor antagonist) on the contractile responses of the electrically driven rat right ventricle strip to isoprenaline and on the relaxant responses of the rat aorta to procaterol, have been studied. Racemic and (-)-celiprolol or BAAM treatment of the ventricle produced non-parallel rightward shifts of the isoprenaline response curves with a reduction in the maximal response. Sotalol produced parallel rightward displacements of the procaterol response curves of the aorta with no effect on the maximal relaxations. Racemic and (+)- and (-)-celiprolol or BAAM treatment of the aorta produced non-parallel rightwards shifts of the procaterol relaxant curves with a reduction in the maximal relaxation. The BAAM data was used to demonstrate that the KA (dissociation constant) for isoprenaline at beta 1-adrenoceptors was 1.46 x 10(-7) M and for procaterol at beta 2-adrenoceptors was 2.34 x 10(-5) M. Calculation of receptor occupancy demonstrated that to produce a maximal response of the rat right ventricle, had to occupy 87% of the beta 1-adrenoceptors. Likewise, for a maximal response of the rat aorta, procaterol had to occupy 81% of the beta 2-adrenoceptors. It is suggested that the use of tissues with small beta-adrenoceptor reserves has shown that (+/-)- and (-)-celiprolol are slowly dissociating, rather than readily reversible, beta-adrenoceptor antagonists.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Auckland, New Zealand.
authors.forename: S A
authors.initials: SA
authors.lastname: Doggrell
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000526:Alprenolol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D017272:Celiprolol; D004558:Electric Stimulation; D004983:Ethanolamines / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D017265:Procaterol; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D013015:Sotalol / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C045331:bromoacetylalprenololmenthane; D000526:Alprenolol; D013015:Sotalol; D017272:Celiprolol; D007545:Isoproterenol; D017265:Procaterol