title: Nebivolol is devoid of intrinsic sympathomimetic activity.
abstract: Nebivolol is a chemically novel, potent and selective beta 1-adrenoceptor-blocking agent that acutely lowers arterial blood pressure in hypertensive patients and rats without depressing, or even enhancing, left ventricular function. These properties could be compatible with a partial agonistic effect of beta-adrenoceptor-blocking agents. It was the aim of the present study to investigate whether nebivolol has intrinsic sympathomimetic properties. The study was performed on reserpinized dogs and spontaneously hypertensive rats, and on various isolated tissues from various species. Unlike pindolol and practolol, nebivolol did not exert a stimulating effect on the heart rate and left ventricular function in reserpinized animals and/or in isolated atria of reserpinized rats at doses that are clinically active. Nebivolol did not induce relaxation of isolated coronary arteries and saphenous veins at concentrations that block beta-adrenoceptors. These findings indicate that nebivolol is devoid of intrinsic sympathomimetic activity at clinically relevant doses.
authors.affiliation: Department of Cardiovascular Pharmacology, Janssen Research Foundation, Beerse, Belgium.
authors.forename: W J
authors.initials: WJ
authors.lastname: Janssens
authors.forename: A
authors.initials: A
authors.lastname: Van de Water
authors.forename: R
authors.initials: R
authors.lastname: Xhonneux
authors.forename: R S
authors.initials: RS
authors.lastname: Reneman
authors.forename: J M
authors.initials: JM
authors.lastname: Van Nueten
authors.forename: P A
authors.initials: PA
authors.lastname: Janssen
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004562:Electrocardiography; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D000068577:Nebivolol; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology; D013566:Sympathomimetics
chemical_list: D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D013566:Sympathomimetics; D000068577:Nebivolol; D012110:Reserpine