Synephrine
Encyclopedia
Synephrine is a drug
commonly used for weight loss. While its effectiveness is widely debated, synephrine has gained significant popularity as an alternative to ephedrine
, a related substance which has been made illegal or restricted in many countries due to health risks and its use as a precursor in the illicit manufacturing of methamphetamine
. There is however no occurrence of diverted synephrine for the manufacture of amphetamines, and the naturally occurring synephrine is, due to its phenolic group, unsuitable for such diversion. Products containing bitter orange
or synephrine are suspected of causing adverse cardiovascular reactions. Synephrine is derived primarily from the immature fruit of Citrus aurantium, a relatively small citrus tree, of which several of its more common names include Bitter Orange, Sour Orange, and Zhi shi. Dietary supplements generally supply single oral doses of 3–30 mg, while as a pharmaceutical agent it is given orally or by parenteral
injection in 20–100 mg doses as a vasoconstrictor to hypotensive patients.
(neosynephrine), one of its positional isomers
. The chemicals are similar in structure; the only difference is the location of the aromatic hydroxyl group. In synephrine, the hydroxyl is at the para position, whereas in neosynephrine it is at the meta position. Each compound has differing biological properties.
, sometimes with an NSAID. Some reports have indicated that such diet pills cause numerous harmful effects. The Mayo Clinic
published a report that suggested a link between Stacker 2 pills and increased risk of ischemic stroke, increased blood pressure
, and myocardial infarction
(heart attack).
Due to the aromatic hydroxyl group, the pharmacological profile is different to ephedrine; synephrine as a catecholamine
analog is acting predominantly on peripheral adrenergic receptors and does not have a pronounced effect on the CNS
.
Synephrine can also cause arrhythmias. It is similar to ephedrine
and can therefore show similar symptoms (see ephedrine adverse effects).
Following the presentation of a healthy young man with a myocardial infarction, a case study and subsequent literature review found that the makers of "nutritional supplements" who replaced ephedrine
with its analogs p-synephrine and/or p-octopamine from "bitter orange" had in effect simply found a loophole in the FDA's April 2004 regulation banning ephedra in those supplements by substituting a similar substance the regulation did not address, while permitting them to label the products as "ephedra-free".
Unripe, dried fruits from Asian cultivars of Citrus aurantium (TCM: Zhi shi) contain phenylethylamines, mostly synephrine (to about 0.2%). Extracts thereof are today the main source of naturally occurring synephrine.
Synephrine and related alkaloids occur in in citrus
fruit juices, particularly in bitter orange products and certain mandarin cultivars. Concentrations ranged from 55 to 160 mg/L in juice products obtained from the Satsuma mandarin variety.
It can be assumed that trace amounts of synephrine also occur in regular juice products obtained from Citrus aurantium.
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
commonly used for weight loss. While its effectiveness is widely debated, synephrine has gained significant popularity as an alternative to ephedrine
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....
, a related substance which has been made illegal or restricted in many countries due to health risks and its use as a precursor in the illicit manufacturing of methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...
. There is however no occurrence of diverted synephrine for the manufacture of amphetamines, and the naturally occurring synephrine is, due to its phenolic group, unsuitable for such diversion. Products containing bitter orange
Bitter orange
The name "bitter orange", also known as Seville orange, sour orange, bigarade orange, and marmalade orange, refers to a citrus tree and its fruit. Many varieties of bitter orange are used for their essential oil, which is used in perfume and as a flavoring...
or synephrine are suspected of causing adverse cardiovascular reactions. Synephrine is derived primarily from the immature fruit of Citrus aurantium, a relatively small citrus tree, of which several of its more common names include Bitter Orange, Sour Orange, and Zhi shi. Dietary supplements generally supply single oral doses of 3–30 mg, while as a pharmaceutical agent it is given orally or by parenteral
Parenteral
Parenteral is a route of administration that involves piercing the skin or mucous membrane. Parenteral nutrition refers to providing nutrition via the veins.-Etymology:...
injection in 20–100 mg doses as a vasoconstrictor to hypotensive patients.
Claims
- Decreases appetite
- Burns fat
- Increases energy
- Increases metabolismMetabolismMetabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
- Promotes weight loss
- Increases body heat
Synephrine and neosynephrine
There has been some confusion surrounding synephrine and phenylephrinePhenylephrine
Phenylephrine is a selective α1-adrenergic receptor agonist used primarily as a decongestant, as an agent to dilate the pupil, and to increase blood pressure...
(neosynephrine), one of its positional isomers
Structural isomerism
Structural isomerism, or constitutional isomerism , is a form of isomerism in which molecules with the same molecular formula have bonded together in different orders, as opposed to stereoisomerism. There are multiple synonyms for constitutional isomers.Three categories of constitutional isomers...
. The chemicals are similar in structure; the only difference is the location of the aromatic hydroxyl group. In synephrine, the hydroxyl is at the para position, whereas in neosynephrine it is at the meta position. Each compound has differing biological properties.
- Phenylephrine acts primarily on alpha1 adrenergic receptors, so it has mainly vasoconstricting actions.
- Synephrine's pharmacologyPharmacologyPharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
has not been thoroughly studied. Some comparisons with octopamineOctopamineOctopamine is an endogenous biogenic amine that is closely related to norepinephrine, and has effects on the adrenergic and dopaminergic systems. It is also found naturally in numerous plants, including bitter orange. Biosynthesis of the D--enantiomer of octopamine is by β-hydroxylation of...
have been performed. There is some evidence that it may act at β3 adrenergic receptorsBeta-3 adrenergic receptorThe beta-3 adrenergic receptor , also known as ADRB3, is an beta-adrenergic receptor, and also denotes the human gene encoding it.-Function:Actions of the β3 receptor include:*Enhancement of lipolysis in adipose tissue....
.
Associated risks
Many diet products such as "Stacker 2", "Xenadrine-EFX", etc. contain a "stack" of synephrine along with caffeineCaffeine
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
, sometimes with an NSAID. Some reports have indicated that such diet pills cause numerous harmful effects. The Mayo Clinic
Mayo Clinic
Mayo Clinic is a not-for-profit medical practice and medical research group specializing in treating difficult patients . Patients are referred to Mayo Clinic from across the U.S. and the world, and it is known for innovative and effective treatments. Mayo Clinic is known for being at the top of...
published a report that suggested a link between Stacker 2 pills and increased risk of ischemic stroke, increased blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
, and myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
(heart attack).
Due to the aromatic hydroxyl group, the pharmacological profile is different to ephedrine; synephrine as a catecholamine
Catecholamine
Catecholamines are molecules that have a catechol nucleus consisting of benzene with two hydroxyl side groups and a side-chain amine. They include dopamine, as well as the "fight-or-flight" hormones adrenaline and noradrenaline released by the adrenal medulla of the adrenal glands in response to...
analog is acting predominantly on peripheral adrenergic receptors and does not have a pronounced effect on the CNS
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
.
Synephrine can also cause arrhythmias. It is similar to ephedrine
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....
and can therefore show similar symptoms (see ephedrine adverse effects).
Following the presentation of a healthy young man with a myocardial infarction, a case study and subsequent literature review found that the makers of "nutritional supplements" who replaced ephedrine
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....
with its analogs p-synephrine and/or p-octopamine from "bitter orange" had in effect simply found a loophole in the FDA's April 2004 regulation banning ephedra in those supplements by substituting a similar substance the regulation did not address, while permitting them to label the products as "ephedra-free".
Natural occurrence
It is reported as naturally occurring in the following species: Coryphanta cornifera, C. durangensis, C. elephantides, C. greenwoodii, C. ottonis, C. pectinata, C. poselgeriana, C ramillosa, C. runyonii, Dolichothele sphaerica, D. surculosa, D. uberiformis.Unripe, dried fruits from Asian cultivars of Citrus aurantium (TCM: Zhi shi) contain phenylethylamines, mostly synephrine (to about 0.2%). Extracts thereof are today the main source of naturally occurring synephrine.
Synephrine and related alkaloids occur in in citrus
Citrus
Citrus is a common term and genus of flowering plants in the rue family, Rutaceae. Citrus is believed to have originated in the part of Southeast Asia bordered by Northeastern India, Myanmar and the Yunnan province of China...
fruit juices, particularly in bitter orange products and certain mandarin cultivars. Concentrations ranged from 55 to 160 mg/L in juice products obtained from the Satsuma mandarin variety.
It can be assumed that trace amounts of synephrine also occur in regular juice products obtained from Citrus aurantium.