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Celiprolol: A beta‐1 partial agonist in isolated cat cardiac tissue

The cardiostimulatory effects of celiprolol were evaluated in isolated cat cardiac tissue to elucidate the contributions of beta versus alpha adrenoceptor mechanisms. Racemic celiprolol increased the spontaneous rate of cat right atria and the developed tension of paced left hemi‐atria and papillary muscle 44% ± 7%, 36% + 5% and approximately 23% of the maximum response to isoproterenol, respectively. In both left and right atrial preparations, celiprolol (d‐, l‐, and racemic) produced a concentration‐related cardiostimulatory effect. The l‐ and racemic celiprolol were approximately 50 times more potent than the d‐isomer. The cardiostimulatory effects of celiprolol in cat right atria were either not changed, or only slightly reduced, by catecholamine depletion with reserpine or chemical sympathectomy with 6‐hydroxydopamine or by alpha blockade with prazosin (3 × 10−7 M) alone or in combination with propranolol. Beta‐1 blockade with atenolol 10−6 M alone produced a parallel rightward shift of the celiprolol concentration‐response curve of 1.7 log units. By contrast, beta‐2 blockade with ICI 118, 551 10−6 M shifted the celiprolol response curve only 0.6 log units. It is concluded that celiprolol has a limited but significant cardiostimulatory effect in isolated cat cardiac tissue due primarily to a partial agonist action on postsynaptic beta‐1 receptors and does not involve noradrenergic mechanisms either preor postsynaptically.