The Effects of (±)-, (+)- and (-)-Celiprolol and Bromoacetylalprenololmentane at the β-Adrenoceptors of Rat Isolated Cardiovascular Preparations

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Abstract
The effects of (±)-, (+)- and (-)-celiprolol and of bromoacetylalprenololmentane (BAAM, an irreversible β-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 β1-adrenoceptors was 1.46 × 10−7 M and for procaterol at β2-adrenoceptors was 2.34 × 10−5 M. Calculation of receptor occupancy demonstrated that to produce a maximal response of the rat right ventricle, isoprenaline had to occupy 87% of the β1-adrenoceptors. Likewise, for a maximal response of the rat aorta, procaterol had to occupy 81 % of the β2-adrenoceptors. It is suggested that the use of tissues with small β-adrenoceptor reserves has shown that (±)- and (-)-celiprolol are slowly dissociating, rather than readily reversible, β-adrenoceptor antagonists.