The l-enantiomer of nebivolol potentiates the blood pressure lowering effect of the d-enantiomer.
In this study the effect of l-nebivolol on the blood pressure lowering action of d-nebivolol was investigated after intraperitoneal administration of the drugs to spontaneously hypertensive rats. Doses of l-nebivolol which did not affect blood pressure when given alone potentiated the decrease in systolic and diastolic blood pressure induced by 1.25 mg.kg-1 d-nebivolol. The potentiating effect of l-nebivolol was seen at doses higher than 0.16 mg.kg-1. At 1.25 mg.kg-1 d-nebivolol significantly reduced the heart rate, an effect which was not potentiated by l-nebivolol in doses up to 1.25 mg.kg-1. Higher doses of l-nebivolol (2.5 and 5.0 mg.kg-1) in combination with 1.25 mg.kg-1 d-nebivolol not only lowered the blood pressure further, but also significantly reduced the heart rate; thus at these doses the enantiomers together exerted more pronounced beta 1-adrenoceptor blocking properties. This is probably disadvantageous, because d,l-nebivolol has been shown to decrease arterial blood pressure in hypertensive patients and animals before it reaches its maximal beta 1-adrenoceptor blocking effect. Therefore, the racemic mixture of 50% d-nebivolol and 50% l-nebivolol seems to contain the two compounds in near optimal proportions for an antihypertensive effect.
Xhonneux
R
R
Cardiovascular Department, Janssen Research Foundation, Beerse Belgium.
Wouters
L
L
Reneman
R S
RS
Janssen
P A
PA
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents; D001578:Benzopyrans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004983:Ethanolamines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D000068577:Nebivolol; D051381:Rats; D011918:Rats, Inbred SHR; D013237:Stereoisomerism
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol