Synephrine hydrochloride
[CAS# 5985-28-4]

Identification

• Classification: Biochemical >> Inhibitor >> Neuronal signaling >> Adrenergic receptor agonist
• Name: Synephrine hydrochloride
• Synonyms: 1-(4-Hydroxyphenyl)-2-(methylamino)-ethanol hydrochloride
• Molecular Formula: C₉H₁₃NO₂.HCl
• Molecular Weight: 203.67
• CAS Registry Number: 5985-28-4
• EC Number: 227-804-6
• SMILES: CNCC(C1=CC=C(C=C1)O)O.Cl

Properties

• Solubility: DMSO: 52mg/mL (Expl.)

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2A	H319
Eye irritation	Eye Irrit.	2	H319

Discovery and Applications

Synephrine hydrochloride is a naturally occurring protoalkaloid primarily found in the fruits of Citrus aurantium (bitter orange) and other citrus species. Chemically, it is a phenethylamine derivative with a hydroxyl group on the para position of the aromatic ring and an amine functional group, which is protonated in the hydrochloride salt form to improve stability and solubility. Synephrine hydrochloride has been studied for its pharmacological properties, including sympathomimetic, metabolic, and cardiovascular effects.

The discovery of synephrine dates back to the early 20th century when chemists were investigating the bioactive constituents of citrus plants. Its isolation and structural elucidation were achieved using chromatographic techniques and spectroscopic analysis. The hydrochloride form was developed to stabilize the compound and facilitate its use in pharmacological studies and clinical applications.

Pharmacologically, synephrine hydrochloride acts as a sympathomimetic agent, primarily stimulating adrenergic receptors, including beta-3 adrenergic receptors. This action leads to increased energy expenditure, lipolysis, and thermogenesis, which has prompted research into its potential use for weight management and metabolic enhancement. Additionally, synephrine can influence cardiovascular parameters such as heart rate and blood pressure, although these effects are generally milder compared to other structurally related sympathomimetics, such as ephedrine.

In metabolic studies, synephrine hydrochloride has demonstrated the ability to promote fat oxidation and improve energy metabolism, supporting its use as a component in dietary supplements aimed at weight management. Its mechanism involves stimulation of lipolysis in adipose tissue and modulation of metabolic enzymes, which enhances the mobilization and utilization of stored fat.

Synephrine hydrochloride also exhibits potential effects on gastrointestinal motility and smooth muscle activity. Historically, extracts of bitter orange containing synephrine were used in traditional medicine to treat digestive issues, and contemporary research has explored its prokinetic and spasmolytic properties. These actions are thought to be mediated through adrenergic receptor modulation and direct effects on smooth muscle cells.

Safety and pharmacokinetics of synephrine hydrochloride have been studied in both preclinical and clinical settings. The compound is generally well tolerated at moderate doses, with transient side effects such as mild increases in blood pressure or heart rate. Its oral bioavailability allows effective absorption, and the hydrochloride form ensures stability and consistent dosing.

In addition to weight management and metabolic applications, synephrine hydrochloride has been investigated for its potential in enhancing athletic performance and reducing fatigue through increased energy expenditure and improved circulation. However, these effects require careful monitoring due to variability in individual cardiovascular responses.

Overall, synephrine hydrochloride is a bioactive protoalkaloid with sympathomimetic, metabolic, and mild cardiovascular effects. Its historical use in traditional medicine, combined with modern studies on adrenergic receptor modulation and energy metabolism, highlights its potential applications in weight management, metabolic enhancement, and gastrointestinal support.

References

2025. Quantitative in vitro-to-in vivo extrapolation of human adrenergic and trace amine-associated receptor 1 potencies of pre-workout supplement ingredients using physiologically based kinetic modelling-based reverse dosimetry. Archives of Toxicology, 99(4).
DOI: 10.1007/s00204-025-03992-7

2024. Evaluation of deep eutectic solvents chiral selectors based on lactobionic acid in capillary electrophoresis. Analytical and Bioanalytical Chemistry, 416(9).
DOI: 10.1007/s00216-024-05138-7

2011. Isopropylnorsynephrine is a stronger lipolytic agent in human adipocytes than synephrine and other amines present in Citrus aurantium. Journal of Physiology and Biochemistry, 67(3).
DOI: 10.1007/s13105-011-0078-2