A Review of the Receptor-Binding Properties ofp-Synephrine as Related to Its Pharmacological Effects

Abstract

Bitter orange (Citrus aurantium) extract and its primary protoalkaloid p-synephrine are used widely in weight loss/weight management and sports performance products. Because of structural similarities, the pharmacological effects of p-synephrine are widely assumed to be similar to those of ephedrine, m-synephrine (phenylephrine), and endogenous amine neurotransmitters as norepinephrine and epinephrine. However, small structural changes result in the receptor binding characteristics of these amines that are markedly different, providing a plausible explanation for the paucity of adverse effects associated with the wide-spread consumption of p-synephrine in the form of dietary supplements as well as in various Citrus foods and juices. This paper summarizes the adrenoreceptor binding characteristics of p-synephrine relative to m-synephrine, norepinephrine, and other amines as related to the observed pharmacological effects.

Obesity and Clinical Riskiness Relationship: Therapeutic Management by Dietary Antioxidant Supplementation—a Review

“…The issue of safety and efficacy is further clouded and complicated by the structural similarity of p-synephrine to ephedrine and other biogenic amines. In spite of the fact that the pharmacokinetics of these compounds and their receptor binding specificities are vastly different due to significant structural and stereochemical differences [88].…”

Increased eating control and energy levels associated with consumption of bitter orange (<em>p</em>-synephrine) extract: a randomized placebo-controlled study

“…6 In general, p-synephrine exhibits little or no binding to α1, α2, β1, and β2-adrenergic receptors and, therefore, it does not and would not be expected to exert significant cardiovascular effects.…”

Stereochemical and pharmacological differences between naturally occurring p-synephrine and synthetic p-synephrine

“…However, the d-form of p-synephrine exhibited essentially no binding to these b-adrenoreceptors, while the l-form of psynephrine exhibited very low binding affinity relative to nor-epinephrine, indicating that it would exhibit very little cardiovascular activity. The lipolytic activity of p-synephrine is believed to be due to binding to b-3 adrenoreceptors in tissues (Stohs, Preuss, & Shara, 2011b). Brown et al (1988) examined the binding activities of the land d-forms of p-synephrine and m-synephrine to a1-adrenoreceptors in rat aorta and a2-adrenoreceptors from rabbit saphenous vein.…”

“…Thus, m-synephrine will bind to and activate the receptor resulting in vasoconstriction and an increase in blood pressure, while p-synephrine would have little or no effect. As a consequence, p-synephrine would be expected to have little effect on blood pressure relative to m-synephrine or nor-epinephrine (Stohs et al, 2011a(Stohs et al, , 2011b.…”