[Intrinsic sympathomimetic action and its special features as demonstrated by the beta-1-receptor blocker celiprolol]

The Intrinsic Sympathetic Activity (ISA) of the beta-1-adrenoceptor blocker celiprolol was tested in a series of pharmacological and clinical investigations. Celiprolol shows much more pronounced positive chronotropic effects in spontaneously beating atria of cats than in those of guinea-pigs and rats. Positive inotropic effects of celiprolol are much pronounced in the left kitten atrium, but scarcely demonstrable in the kitten papillary muscle. Celiprolol has no influence on the adenylyl cyclase activity of the dog heart. In reserpinized rats and reserpinized, adrenalectomized, vagotomized cats celiprolol increases the heart rate to the same extent as the beta-blocker pindolol. In ganglion-blocked dogs celiprolol distinctly increases heart rate and left ventricular contraction force. Celiprolol relaxes isolated human arterial and venous strips and induces a transient increase of the femoral arterial blood flow in anaesthetized dogs. Celiprolol relaxes isolated bovine tracheal muscle preparations and reduces the airway resistance in anaesthetized cats infused with serotonin. The intrinsic chronotropic effects of celiprolol in cat atria in vitro and in reserpinized rats in vivo and the relaxing effects of celiprolol in isolated bovine tracheal muscles are antagonized by propranolol, and therefore these actions may be explained by the ISA of celiprolol. However the vascular relaxing effects of celiprolol in vitro and in vivo and the bronchodilating effects in the serotonin-infused cat are not blocked by propranolol. In order to obtain a more precise characterization of these surprising effects, further pharmacological investigations were done. In the isolated femoral artery of the dog the concentration-response curve of calcium chloride is not influenced by celiprolol while it is antagonized by verapamil. A serotonin antagonistic effect cannot be demonstrated for celiprolol either in receptor binding studies or on the blood pressure of anaesthetized dogs. Celiprolol inhibits the methacholine bronchospasm in rats and the prostaglandin F2 alpha-induced bronchoconstriction in cats. The histamine-induced bronchoconstriction in dogs is scarcely affected by celiprolol while it is enhanced by propranolol. In radioligand studies celiprolol shows a tenfold higher affinity for alpha-2 in comparison to alpha-1 receptors. Celiprolol enhances the inhibitory effect of clonidine in the electrically stimulated vas deferens of the rat in vitro.(ABSTRACT TRUNCATED AT 400 WORDS)