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Octopamine: Alternative for Ephedra or the Latest Snakeoil?

Octopamine: Alternative for Ephedra or the Latest Snakeoil?, By: Annsi Manninen Obesity drugs act by a variety of mechanisms, but all must either reduce energy intake and/or increase energy output. Energy intake may be curbed by reducing hunger or appetite or by enhancing satiety. Obesity drugs also may increase activity levels or stimulate metabolic rate. The non-prescription weigh-loss market in the U.S. is flooded with many hundreds of products that promised to shed pounds quickly and easily. Few data, however, support their efficacy or safety as agents for weight reduction and long-term maintenance of weight loss. The latest ingredient in diet supplements is octopamine, a biogenic amine. Octopamine shares structural and functional homologies with noradrenaline. Molecular Nutrition claims that “ Octopamine is a potent naturally occurring selective beta-3 adrenergic receptor agonist, and has been shown in in-vitro animal studies to exhibit strong lipolytic [fat mobilizing] activity in fat cells. It is also the first selective beta-3 agonist ever to be isolated and made available as a nutritional supplement, and given the understanding we have of beta-3 receptors and their ability to mediate human fat loss we believe it holds tremendous promise as a powerful, comfortable and safe fat-loss alternative to a non-selective beta agonist like ephedrine.“ This article examines some of the science behind octopamine. Beta-Receptors and Lipolysis The major function of adipose tissue (fat tissue) is storage of the triglycerides (neutral fat) until they are needed to provide energy elsewhere in the body. The first stage in using triglycerides for energy is hydrolysis (lipolysis) of the triglycerides into fatty acids and glycerol. Then, both the fatty acids and the glycerol are transported in the blood to the active tissues, where they will be oxidized (burned) for energy. Lipolysis is stimulated by catecholiamines (norepinephrine and epinephrine). The effects of norepinephrine and epinephrine are brought about by actions of on two classes of receptors, alpha- and beta-adrenergic receptors. Beta-receptors are subdivided into three groups, beta1-, beta2-, and beta3-receptors. During the last decade, intensive research into the rodent beta3-receptor has led to the synthesis of numerous beta3-agonists (e.g., BRL 37,344, CL 316,243, SR 58,611) that are potent stimulators of thermogenesis in brown fat tissue and lipolysis in white fat tissue (“lard”). However, the physiological catecholamines (norepinephrine, epinephrine) have less affinity for the beta3-receptors than for the beta1– or beta2-receptors. Thus, it is widely accepted that adrenaline and noradrenaline cannot exert their beeta3-adrenergic effects independently of their beta1- and beta2-receptor-mediated actions, since the three subtypes of receptors co-exits (in different properties) in most of the tissues which respond to selective beta3-receptor agonists. This has led scientist to investigate the beta-adrenergic properties of several biogenic amines such as octopamine, tyramine, synephrine, beta-phenylethylamine, epinine, phenylethanolamine and dopamine. Most of them are metabolically related to catecholamines, share common precursors, formation and degradation, and can be intercorverted into norepinephrine or epinephrine. Octopamine and Lipolysis in Human Fat Cells In rodents, lipolysis is know to be stimulated mainly by the activation of beta-3-receptors in white fat cells, but beta1- and beta2-agonists can also stimulate lipolysis. However, white fat cells from primates – including humans – exhibit only weak activation of lipolysis in response to beta3-agonist while they respond to beta1- and beta2-agonist.1 To explore the efficacy and potency of the above mentioned biogenic amines on the various subtypes of beta-receptors coexisting on the same cell, Dr. Christina Carpene and colleagues from France used isolated fat cells as a model exhibiting, with large interspecific differences, various proportions of all the beta-receptors subtypes involved in the control of lipolysis.2 Results indicated that octopamine fully stimulated lipolysis, but only in rat, hamster and dog fat cells. In human fat cells, octopamine stimulated lipolysis only very weakly. Bottom Line If you are rat, hamster or dog, octopamine holds some promise. However, it does not appear to exhibit strong lipolytic activity in human fat cells. Also, safety of octopamine is unknown. Clearly, well-controlled human studies are needed before any conclusions can be drawn.

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