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

Eur J Pharmacol. 1990 Jun 8;181(3):261-5. doi: 10.1016/0014-2999(90)90087-m.

Abstract

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.

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Antihypertensive Agents*
  • Benzopyrans / pharmacology*
  • Blood Pressure / drug effects*
  • Ethanolamines / pharmacology*
  • Heart Rate / drug effects
  • Nebivolol
  • Rats
  • Rats, Inbred SHR
  • Stereoisomerism

Substances

  • Adrenergic beta-Antagonists
  • Antihypertensive Agents
  • Benzopyrans
  • Ethanolamines
  • Nebivolol