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Octopamine (Norsynephrine HCL)

Moderate weight-lowering effect of octopamine treatment in obese Zucker rats.
Galitzky J, Carpene C, Lafontan M, Berlan M.

Institut National de la Santé et de la Recherche Médicale, U586, CHU Rangueil, Université Paul Sabatier, 31043 Toulouse, France.

Octopamine is proposed as a substitution product of synephrine by diverse drug industries that advertise new weight-lowering products or medicinal plants enriched in this biogenic amine. We have already reported that octopamine is able to activate in vitro lipolysis in rat adipocytes via beta3-adrenergic receptor activation, while it activates glucose uptake in human fat cells via its oxidation by amine oxidases. In this work, we tested whether a chronic challenge with octopamine could exert anti-obesity effects. A treatment consisting in daily i.p. administration of octopamine (81 micromol/kg) was compared on a four-week period with calorie restriction in the genetically obese Zucker rat. Octopamine treatment resulted in a 19% decrease in body weight gain, when compared to the 177 g gained by controls during the same period. The decrease in body weight gain was detectable only after three weeks of treatment and was apparently not due to a pronounced and sustainable anorectic effect of octopamine since: 1) cumulated food consumption was only reduced by 10%; 2) the experimental 18% reduction of food intake provoked a rapid decrease in body weight gain, significant in less than two weeks. The lipolytic responses to isoprenaline or octopamine and the stimulation of glucose transport by insulin or by the amine oxidase substrate tyramine were unmodified by the treatments. Noteworthy, the elevated plasma insulin of obese rats was lowered by octopamine. This study shows that octopamine can reduce body weight gain in obese rats, without apparent adverse effects, but with less efficacy than beta3-AR agonists.

A new subtype of beta-adrenoceptor (beta 3) has been recently characterized in human and rodent genome. This receptor can be stimulated with catecholamines or selective pharmacological beta 3-adrenoceptor agonists and it fulfils similar function of norepinephrine in rodent and dog adipose tissue. Octopamine but not tyramine or phenylethylamine activated lipolysis in dog fat cells as well as BRL 37344 (a beta 3-adrenoceptor agonist) or norepinephrine. In human fat cells, norepinephrine was lipolytic whereas BRL 37344 or octopamine were without effect. The lipolytic effect of octopamine did not depend on beta 1-/beta 2-adrenoceptor stimulation since it was not suppressed by beta 1- or beta 2-antagonists. These results suggest that octopamine is a specific endogenous ligand for beta 3-adrenoceptors in mammals.

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