Isopropylnorsynephrine is a stronger lipolytic agent in human adipocytes than synephrine and other amines present in Citrus aurantium

J Physiol Biochem. 2011 Sep;67(3):443-52. doi: 10.1007/s13105-011-0078-2. Epub 2011 Feb 19.


The weight loss observed in consumers of extracts of Citrus aurantium (bitter orange) has been tentatively attributed to the lipolytic and thermogenic effects of the alkaloids abundant in the unripe fruit. Synephrine, octopamine, tyramine, and other alkaloids have been repeatedly identified and quantified in Citrus members of the Rutaceae family or in their extracts incorporated in dietary supplements for weight management. However, there are only scarce reports on their lipolytic action. This study aimed at comparing the acute lipolytic activity of synephrine, octopamine, tyramine, and N-methyltyramine in rat and human adipocytes. Maximal response to the prototypical β-adrenergic agonist isoprenaline was taken as reference in both species. In rat, octopamine was slightly more active than synephrine while tyramine and N-methyl tyramine did not stimulate-and even inhibited-lipolysis. In human adipocytes, none of these amines stimulated lipolysis when tested up to 10 μg/ml. At higher doses (≥100 μg/ml), tyramine and N-methyl tyramine induced only 20% of the maximal lipolysis and exhibited antilipolytic properties. Synephrine and octopamine were partially stimulatory at high doses. Since synephrine is more abundant than octopamine in C. aurantium, it should be the main responsible for the putative lipolytic action of the extracts claimed to mitigate obesity. Noteworthy, their common isopropyl derivative, isopropylnorsynephrine (also named isopropyloctopamine or betaphrine), was clearly lipolytic: active at 1 μg/ml and reproducing more than 60% of isoprenaline maximal effect in human adipocytes. This compound, not detected in C. aurantium, and which has few reported adverse effects to date, might be useful for in vivo triglyceride breakdown.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes, White / drug effects*
  • Adipocytes, White / metabolism
  • Adipose Tissue, White / drug effects
  • Adipose Tissue, White / metabolism
  • Animals
  • Citrus / chemistry*
  • Epinephrine / pharmacology
  • Female
  • Glucose / metabolism
  • Humans
  • Isoproterenol / pharmacology
  • Lipolysis / drug effects*
  • Lipotropic Agents / pharmacology*
  • Monoamine Oxidase / metabolism
  • Octopamine / analogs & derivatives*
  • Octopamine / chemistry
  • Octopamine / pharmacology
  • Oxidation-Reduction
  • Plant Extracts / pharmacology*
  • Rats
  • Rats, Wistar
  • Synephrine / pharmacology*
  • Tyramine / analogs & derivatives
  • Tyramine / pharmacology


  • Lipotropic Agents
  • Plant Extracts
  • Octopamine
  • deterenol
  • Monoamine Oxidase
  • methyl-4-tyramine
  • Glucose
  • Isoproterenol
  • Synephrine
  • Tyramine
  • Epinephrine