Cardiovascular effects of dl-nebivolol and its enantiomers--a comparison with those of atenolol.
In the present study, we investigated the cardiovascular effects of dl-nebivolol, a newly synthetized, chemically novel, beta 1-adrenoceptor antagonist and its enantiomers, d-nebivolol (SRRR) and l-nebivolol (RSSS), in closed-chest anesthetized dogs, using atenolol as a reference substance. Results from preliminary studies in vitro indicate that d-nebivolol is the beta 1-adrenoceptor antagonist and that l-nebivolol is practically devoid of beta-adrenoceptor-blocking properties. Unlike atenolol, dl-nebivolol does not depress left ventricular function and slightly, but significantly, reduces peripheral vascular resistance over the dose range from 0.0025 to 0.04 mg.kg-1 i.v. These observations are likely to be clinically relevant because one daily oral dose of 5 mg dl-nebivolol effectively lowers arterial blood pressure in patients with hypertension. The favorable hemodynamic profile of dl-nebivolol can be ascribed to the l-enantiomer because the cardiovascular effects of this enantiomer are similar to those of the racemate. The cardiovascular profile of the d-enantiomer is similar to that of atenolol, albeit that its depressant effect on left ventricular function occurs at higher doses.
Van de Water
A
A
Cardiovascular Department, Janssen Research Foundation, Beerse, Belgium.
Xhonneux
R
R
Reneman
R S
RS
Janssen
P A
PA
D000818:Animals; D001262:Atenolol / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D004285:Dogs; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D000068577:Nebivolol; D013237:Stereoisomerism
D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D001262:Atenolol