CARDIOVASCULAR EFFECTS OF INTRACEREBROVENTRICULAR INJECTIONS OF (+/-)-NEBIVOLOL AND ITS ENANTIOMERS - A COMPARISON WITH THOSE OF METOPROLOL IN THE RAT

The cardiovascular effects of (+/-)-nebivolol, a potent beta-1-adrenoceptor antagonist, and its enantiomers, (+)-nebivolol (SRRR) and (-)-nebivolol (RSSS) in normotensive anaesthetized rats, have been investigated using metoprolol as a reference substance. The drugs decreased blood pressure and heart rate immediately after i.c.v. injection. These effects paralleled the beta-blocking potencies ((+)- > (+/-)- > (-)- nebivolol). Metoprolol induced a weaker hypotension than (+/-)-nebivolol, and a long-lasting reduction in stroke volume. As reported after i.v. administration, (+/-)-nebivolol and isomers by the i.c.v. route decreased peripheral vascular resistance following i.c.v. administration while metoprolol increased it. These effects are centrally mediated since cardiovascular responses to isoprenaline i.v. remained unchanged.