Alpha 2-adrenoceptor antagonist potencies of two hydroxylated metabolites of yohimbine

Br J Pharmacol. 1993 Apr;108(4):927-32. doi: 10.1111/j.1476-5381.1993.tb13488.x.


1. The alpha 2-adrenoceptor antagonist capacities of two hydroxylated metabolites of yohimbine in man (10-OH-yohimbine and 11-OH-yohimbine) were investigated on the alpha 2-adrenoceptors of human platelets and adipocytes and compared to those of yohimbine. 2. Yohimbine and 11-OH-yohimbine exhibited similar alpha 2-adrenoceptor affinity in biological studies i.e. inhibition of adrenaline-induced platelet aggregation and inhibition of UK14304-induced antilipolysis in adipocytes. 3. Yohimbine and the two metabolites displaced [3H]-RX 821002 binding with equivalent affinities in platelet and adipocyte membranes with the following order of potency: yohimbine > 11-OH-yohimbine > 10-OH-yohimbine. However, when binding studies were carried out in binding buffer supplemented with 5% albumin, the apparent affinity of yohimbine was reduced about 10 fold and was similar to that of 11-OH-yohimbine. 4. Yohimbine and its metabolites were bound to different extents to plasma proteins, the bound fraction being 82%, 43% and 32% respectively for yohimbine, 11-OH-yohimbine and 10-OH-yohimbine. 5. These results show that the main hydroxylated metabolite of yohimbine in man (11-OH-yohimbine) possesses alpha 2-adrenoceptor antagonist properties. The discrepancies found in binding studies (i.e. 10 fold lower affinity of 11-OH-yohimbine than yohimbine for alpha 2-adrenoceptors but similar capacities in blocking biological alpha 2-adrenoceptor effects in cells) are attributable to the higher degree of binding of yohimbine to plasma protein.

MeSH terms

  • Adipose Tissue / cytology
  • Adipose Tissue / drug effects
  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology*
  • Blood Platelets / drug effects
  • Blood Proteins / metabolism
  • Brimonidine Tartrate
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Dioxanes / metabolism
  • Epinephrine / pharmacology
  • Humans
  • Hydroxylation
  • Idazoxan / analogs & derivatives
  • In Vitro Techniques
  • Lipolysis / drug effects
  • Male
  • Platelet Aggregation / drug effects
  • Protein Binding
  • Quinoxalines / pharmacology
  • Yohimbine / analogs & derivatives
  • Yohimbine / metabolism
  • Yohimbine / pharmacology*


  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Blood Proteins
  • Dioxanes
  • Quinoxalines
  • 11-hydroxyyohimbine
  • Yohimbine
  • 10-hydroxyyohimbine
  • Brimonidine Tartrate
  • 2-methoxyidazoxan
  • Idazoxan
  • Epinephrine