Phenylephrine hydrochloride
[CAS# 61-76-7]

Identification

• Classification: API >> Circulatory system medication >> Anti-shock vasoactive drug
• Name: Phenylephrine hydrochloride
• Synonyms: L(-)-Phenylephrine hydrochloride; (R)-(-)-1-(3-Hydroxyphenyl)-2-methylaminoethanol hydrochloride; 3-Hydroxy-alpha-(methylaminomethyl)benzyl alcohol
• Molecular Formula: C₉H₁₃NO₂.HCl
• Molecular Weight: 203.67
• CAS Registry Number: 61-76-7
• EC Number: 200-517-3
• SMILES: CNC[C@@H](C1=CC(=CC=C1)O)O.Cl

Properties

• Melting point: 143 - 145 °C (Expl.)
• Solubility: water: 100 mM, DMSO: 43mg/mL (Expl.)
• Alpha: -47 ° (c=2, H2O) (Expl.)

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H312-H315-H317-H319-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P272-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P317-P319-P321-P330-P332+P317-P333+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Skin sensitization	Skin Sens.	1B	H317
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	4	H312
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Reproductive toxicity	Repr.	2	H361
Specific target organ toxicity - single exposure	STOT SE	2	H371
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Acute toxicity	Acute Tox.	3	H301
Reproductive toxicity	Repr.	1B	H360D
Acute hazardous to the aquatic environment	Aquatic Acute	2	H401
Skin sensitization	Skin Sens.	1	H317

Discovery and Applications

Phenylephrine hydrochloride is a sympathomimetic drug primarily used as a nasal decongestant, vasoconstrictor, and mydriatic agent. Chemically, it is the hydrochloride salt of phenylephrine, with the molecular formula C₉H₁₃NO₂·HCl. The compound features a phenethylamine backbone substituted with a hydroxyl group on the aromatic ring and a hydroxyl group on the side chain, contributing to its biological activity.

Phenylephrine acts mainly as a selective alpha-1 adrenergic receptor agonist. By stimulating these receptors on vascular smooth muscle, it induces vasoconstriction, leading to increased vascular resistance and reduced blood flow in certain tissues. This mechanism underlies its clinical use in relieving nasal congestion by shrinking swollen nasal mucosa and in elevating blood pressure in hypotensive states.

The drug can be administered via multiple routes, including oral, topical (nasal sprays or drops), and parenteral (intravenous or intramuscular) forms. Its onset of action and duration vary depending on the route, with topical applications providing localized effects with minimal systemic exposure.

Phenylephrine hydrochloride is structurally related to other sympathomimetic amines such as epinephrine and norepinephrine but exhibits greater selectivity for alpha-1 receptors and limited beta-adrenergic activity. This selectivity reduces the risk of cardiac side effects associated with beta receptor stimulation.

Pharmacokinetically, phenylephrine undergoes rapid metabolism primarily by monoamine oxidase enzymes in the gastrointestinal tract and liver, resulting in relatively low oral bioavailability. Its metabolites are excreted via the kidneys. The drug has a short plasma half-life, necessitating frequent dosing for sustained effects.

Clinically, phenylephrine hydrochloride is employed to treat nasal congestion caused by allergies, colds, or sinusitis. It is also used to induce pupil dilation during ophthalmic examinations and to increase blood pressure during anesthesia or shock. Additionally, it serves as a component in various combination cold and allergy medications.

Adverse effects are generally mild but can include elevated blood pressure, headache, reflex bradycardia, and, rarely, arrhythmias or ischemic events, especially with excessive dosing or in sensitive individuals. Caution is advised in patients with hypertension, cardiovascular disease, or hyperthyroidism.

In summary, phenylephrine hydrochloride is a selective alpha-1 adrenergic receptor agonist used primarily as a nasal decongestant and vasoconstrictor. Its chemical structure and pharmacological properties enable targeted therapeutic applications with a well-characterized safety profile.

References

1979. Baroreceptor Activation Reduces Reactivity to Noxious Stimulation: Implications for Hypertension. Science, 205(4412).
DOI: 10.1126/science.472749

1979. Effects of sodium nitroprusside and phenylephrine on coronary dynamics in patients with normal left ventricular function. British Heart Journal, 41(4).
DOI: 10.1136/hrt.41.4.456

2024. Punctal Stenosis, Canalicular Obstructions, and Canaliculitis. Oculoplastic, Lacrimal and Orbital Surgery.
DOI: 10.1007/978-3-031-39634-2_46