Alpha 2-antagonist compounds and lipid mobilization: evidence for a lipid mobilizing effect of oral yohimbine in healthy male volunteers

Eur J Clin Invest. 1988 Dec;18(6):587-94. doi: 10.1111/j.1365-2362.1988.tb01272.x.


Investigations were carried out to analyse the interactions of alpha 2-antagonists (yohimbine, idazoxan, SK & F-86,466) with human fat cell alpha 2-adrenoceptors. All the alpha 2-antagonists enhanced the lipolytic potencies of epinephrine with an order of potency: yohimbine greater than idazoxan greater than SK & F-86,466; the same order was also found in 3H-yohimbine competition studies on human fat cell membranes. The most potent agent, yohimbine, was administered orally in humans to define the conditions of appearance and the time-course of a putative lipid-mobilizing action. Oral yohimbine administration (0.2 mg kg-1) elevated plasma glycerol and non-esterified fatty acids in fasting healthy subjects without significant action on heart rate or blood pressure during the time-course of the experiment. The lipid-mobilizing action of yohimbine was reinforced during physical exercise, completely suppressed after a meal and partially blocked by administration of propranolol (0.5 mg kg-1; 60 min before yohimbine). Plasma norepinephrine concentrations were increased (40-50%) after oral yohimbine administration. The rise in plasma catecholamine concentration elicited by yohimbine was not modified by propranolol treatment. The lipid-mobilizing effect of yohimbine could be attributable to: (i) the increase in synaptic norepinephrine with a resultant increment in lipolysis by beta-adrenergic agonism; (ii) a decrease in alpha 2-adrenoceptor stimulation of human fat cell alpha 2-adrenoceptors; (iii) a blockade of presynaptic alpha 2-adrenoceptors. The use of highly selective alpha 2-antagonists will allow investigations into alpha 2-adrenoceptors, which may represent a novel locus for pharmacological intervention in lipid-mobilization strategies.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Adipose Tissue / drug effects*
  • Adipose Tissue / metabolism
  • Adrenergic alpha-Antagonists / pharmacology*
  • Adult
  • Benzazepines / pharmacology
  • Dioxanes / pharmacology
  • Epinephrine / pharmacology
  • Exercise
  • Humans
  • Idazoxan
  • Lipid Mobilization / drug effects*
  • Lipolysis / drug effects
  • Male
  • Yohimbine / pharmacology*


  • Adrenergic alpha-Antagonists
  • Benzazepines
  • Dioxanes
  • Yohimbine
  • Idazoxan
  • benalfocin
  • Epinephrine