The l-enantiomer of nebivolol potentiates the blood pressure lowering effect of the d-enantiomer

Abstract In this study the effect of 1-nebivolol on the blood pressure lowering action of d-nebivolol was investigated after intraperitoneal administration of the drugs to spontaneously hypertensive rats. Doses of 1-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 1-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 1-nebivolol in doses up to 1.25 mg · kg −1 . Higher doses of 1-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 β 1 -drenoceptor blocking properties. This is probably disadvantageous, because d,1-nebivolol has been shown to decrease arterial blood pressure in hypertensive patients and animals before it reaches its maximal β 1 -adrenoceptor blocking effect. Therefore, the racemic mixture of 50% d-nebivolol and 50% 1-nebivolol seems to contain the two compounds in near optimal proportions for an antihypertensive effect.