(-)-ephedrine is a phenethylamine alkaloid that is 2-phenylethanamine substituted by a methyl group at the amino nitrogen and a methyl and a hydroxy group at position 2 and 1 respectively. It has a role as a nasal decongestant, a sympathomimetic agent, a vasoconstrictor agent, a xenobiotic, an environmental contaminant, a plant metabolite and a bacterial metabolite. It is a member of phenylethanolamines and a phenethylamine alkaloid. It is a conjugate base of a (-)-ephedrinium.
Ephedrine was first described in western literature in 1888, as a naturally occurring component of the ephedra plant, along with [pseudoephedrine]. Ephedrine acts as both a direct and indirect sympathomimetic. It is an alpha- and beta-adrenergic receptor agonist; however, it also causes the indirect release of norepinephrine from sympathetic neurons, inhibiting norepinephrine reuptake and displacing more norepinephrine from storage vesicles. Ephedrine is used for its vasoconstrictive, positive chronotropic, and positive inotropic effects. Ephedrine and [phenylephrine] are still used to treat hypotension, but their use in other indications has decreased due to the development of more selective adrenergic agonists. Ephedrine was granted a type 7 FDA Approval on 29 April 2016.
Ephedrine is an alpha-Adrenergic Agonist, and beta-Adrenergic Agonist, and Norepinephrine Releasing Agent. The mechanism of action of ephedrine is as an Adrenergic alpha-Agonist, and Adrenergic beta-Agonist. The physiologic effect of ephedrine is by means of Increased Norepinephrine Activity.
Ephedrine is a natural product found in Ephedra likiangensis, Ephedra pachyclada, and other organisms with data available.
Ephedrine is an alkaloid that is an hydroxylated form of phenethylamineand sympathomimetic amine, with potential bronchodilatory and anti-hypotensive activities. Following administration, ephedrine activates post-synaptic noradrenergic receptors. Activation of alpha-adrenergic receptors in the vasculature induces vasoconstriction, and activation of beta-adrenergic receptors in the lungs leads to bronchodilation.
Ephedrine is only found in individuals who have consumed this drug. Ephedrine is an alpha- and beta-adrenergic agonist that may also enhance release of norepinephrine. It has been used in the treatment of several disorders including asthma, heart failure, rhinitis, and urinary incontinence, and for its central nervous system stimulatory effects in the treatment of narcolepsy and depression. It has become less extensively used with the advent of more selective agonists. [PubChem] Ephedrine is similar in molecular structure to the well-known drugs phenylpropanolamine and methamphetamine, as well as to the important neurotransmitter epinephrine (adrenalin). Chemically, it is an alkaloid with a phenethylamine skeleton found in various plants in the genus Ephedra (family Ephedraceae). It works mainly by increasing the activity of norepinephrine (noradrenalin) on adrenergic receptors. It is most usually marketed as the hydrochloride or sulfate salt.
A phenethylamine found in EPHEDRA SINICA. PSEUDOEPHEDRINE is an isomer. It is an alpha- and beta-adrenergic agonist that may also enhance release of norepinephrine. It has been used for asthma, heart failure, rhinitis, and urinary incontinence, and for its central nervous system stimulatory effects in the treatment of narcolepsy and depression. It has become less extensively used with the advent of more selective agonists.
See also: Ephedrine Hydrochloride (has salt form); Ephedrine Sulfate (has salt form); Ephedra equisetina stem (part of).

Ephedrine is predominantly extracted from the Ephedra species, particularly Ephedra sinica. The extraction process involves isolating the alkaloids from the plant material through various methods, including solvent extraction and chromatography. Additionally, ephedrine can also be synthesized chemically, allowing for controlled production in pharmaceutical settings.

Ephedrine is classified as an alkaloid and a sympathomimetic agent. It is structurally related to other compounds such as pseudoephedrine and methamphetamine, differing primarily in its stereochemistry. The compound can exist in multiple forms, with the (+) enantiomer being more pharmacologically active than its (-) counterpart.

The synthesis of ephedrine can be achieved through various methods, including both natural extraction and chemical synthesis.

Methods

1. Natural Extraction:
   • Extraction from Ephedra plants using organic solvents.
   • Isolation techniques such as liquid-liquid extraction and column chromatography are commonly employed.
2. Chemical Synthesis:
   • Akabori-Momotani Reaction: This method synthesizes ephedrine from N-methylalanine and benzaldehyde, producing distinct isotopic profiles that differentiate it from natural sources .
   • Halogenation and Reduction: A common synthetic route involves halogenation of substituted ethyl phenyl ketones followed by reaction with methylamine. The resulting amino ketone undergoes reduction to yield ephedrine .

Technical Details

The chemical synthesis often requires controlling reaction conditions such as temperature and pH to optimize yields and selectivity towards the desired enantiomer. For instance, using sodium hydride or potassium hydride as reducing agents under controlled temperatures has been shown to yield high purity ephedrine .

Ephedrine has a complex molecular structure that contributes to its pharmacological properties.

Structure

• Chemical Formula: C_10H_15NO
• Molecular Weight: 165.24 g/mol
• Structural Representation:
  • The molecular structure features a phenethylamine backbone with hydroxyl (-OH) and methylamino (-NHCH₃) groups attached.

Data

• Melting Point: Approximately 170 °C
• Solubility: Soluble in water and alcohol but less soluble in non-polar solvents.

Ephedrine participates in several chemical reactions that are significant for its synthesis and degradation.

Reactions

1. Reduction Reactions:
   • Ephedrine can be synthesized via reduction of α-methylaminophenylpropanone using reducing agents like lithium aluminum hydride or sodium borohydride, yielding high enantiomeric purity .
2. Acid-Base Reactions:
   • Ephedrine exists in both free base and salt forms (e.g., hydrochloride), which can be interconverted through acid-base reactions.

Technical Details

The synthesis processes often involve careful control of reaction conditions to favor the formation of specific isomers due to their differing biological activities.

Ephedrine exerts its effects primarily through stimulation of adrenergic receptors.

Process

• Adrenergic Receptor Activation: Ephedrine acts as an agonist at both alpha and beta adrenergic receptors, leading to increased heart rate, bronchodilation, and vasoconstriction.
• Release of Norepinephrine: It promotes the release of norepinephrine from sympathetic nerve endings, enhancing sympathetic nervous system activity.

Data

• Half-Life: Approximately 3 to 6 hours.
• Bioavailability: Around 90% when administered orally.

Understanding the physical and chemical properties of ephedrine is crucial for its applications in medicine.

Physical Properties

• Appearance: White crystalline powder.
• Odor: Odorless.
• Taste: Bitter.

Chemical Properties

• pH Range: Solutions tend to be slightly alkaline.
• Stability: Stable under normal conditions but sensitive to light and moisture.

Ephedrine has diverse applications in both medical and scientific fields.

Scientific Uses

1. Pharmacology: Used as a bronchodilator in asthma treatment due to its ability to relax bronchial muscles.
2. Vasopressor Agent: Employed in clinical settings to manage hypotension during anesthesia.
3. Research Tool: Utilized in studies investigating adrenergic receptor functions and drug interactions due to its well-characterized pharmacological profile.

Traditional Use in Ephedra Species: From Ma Huang to Modern Pharmacology

The medicinal use of Ephedra sinica (known as Ma Huang in traditional Chinese medicine) spans over 5,000 years, with the earliest documented uses appearing in the compendium of Emperor Shen Nung (~2700 BC). Classified among “medium bitterness” herbs, Ephedra stems were primarily employed as circulatory stimulants, antitussives, and antipyretics. The 16th-century text Pents’ao Kang Mu by Li Shih-Chen meticulously described its applications for respiratory ailments, cementing its role in Asian pharmacopeia [1] [7].

Parallel traditions emerged globally:

• Native American communities brewed Ephedra nevadensis and related species into “Mormon tea” or “Indian tea” for ceremonial and therapeutic purposes [6].
• Indian religious sects consumed Ephedra-alcohol preparations (notably using E. intermedia and E. pachyclada) to induce spiritual exhilaration, though the psychoactive contributions of ephedrine versus ethanol remained undefined [7].
• Greco-Roman medicine utilized Ephedra species for managing syphilis and gonorrhea, often through topical applications [7].

The pharmacological foundation of these traditions resided in ephedrine’s sympathomimetic effects—bronchodilation, vasoconstriction, and CNS excitation—though pre-modern practitioners lacked knowledge of the specific alkaloid. The 19th-century export of Ephedra stems from China to Japan enabled later chemical isolation [1].

Table 1: Traditional Uses of Ephedra Species Across Cultures

Region	Species Used	Common Name	Primary Traditional Uses
China	Ephedra sinica	Ma Huang	Asthma, cough, circulatory stimulation
North America	Ephedra nevadensis	Mormon tea	Genitourinary infections, ceremonial use
Indian Subcontinent	Ephedra intermedia	Somlata	Spiritual ceremonies, respiratory ailments
Mediterranean	Ephedra distachya	Sea grape	Antisyphilitic agent, diuretic

Early Isolation and Structural Characterization (1885–1926)

In 1885, Japanese chemist Nagai Nagayoshi achieved the first isolation of crystalline ephedrine from Ephedra sinica, determining its empirical formula (C₁₀H₁₅NO) and basic properties. Despite publishing his findings, the compound attracted minimal pharmaceutical interest for decades due to:

• Technical limitations in purifying stereoisomers (ephedrine vs. pseudoephedrine)
• Dominance of adrenaline (isolated in 1901) as the preferred sympathomimetic [1] [7]

The modern pharmacological era of ephedrine began in the early 1920s when Peking Union Medical College researchers Ko Kuei Chen and Carl F. Schmidt systematically reinvestigated Nagai’s work. They:

• Confirmed ephedrine’s oral bioavailability—unlike adrenaline, which required injection
• Identified distinct α- and β-adrenergic effects, revolutionizing autonomic pharmacology
• Demonstrated clinical efficacy in asthma, hypotension, and nasal congestion

Synonyms: Racemic Ephedrine Hydrochloride
Molecular Weight: 201.69
Formula: C6H5CH(OH)CH(CH3)NHCH3·HCl
A racemic mixture containing both D- and L- forms of ephedrine Hydrochloride.
Applications: Commonly used in controlled pharmaceutical preparations, bronchodilators, and chemical
reference materials.
Buy Ephedrine Sulfate (CAS No. 134-72-5)
Ephedrine Sulfate (CAS No. 134-72-5) For sale
Synonyms: L-(−)-Ephedrine sulfate, Ephedrine hemisulfate salt
Molecular Weight: 428.54
Formula: (C10H15NO)2·H2SO4
A sulfate salt form of ephedrine used primarily as a decongestant and bronchodilator.
Applications: Suitable for pharmaceutical formulations and medicinal chemistry research.
Buy Ephedrine Hydrochloride (CAS No. 50-98-6)

Molecular Weight: 201.69
Formula: C6H5CH[CH(NHCH3)CH3]OH·HCl
The hydrochloride form of natural ephedrine, providing higher stability and solubility.
Applications: Used in antihypotensive and decongestant pharmaceutical formulations.
Buy (1S,2R)-(+)-Ephedrine Hydrochloride (CAS: 24221-86-1)
(1S,2R)-(+)-Ephedrine Hydrochloride (CAS No. 24221-86-1)
Synonyms: D-α-(1-Methylaminoethyl)benzyl alcohol hydrochloride
Molecular Weight: 201.69
Formula: C6H5CH[CH(NHCH3)CH3]OH·HCl
The D-isomer (also known as dextro-ephedrine) of ephedrine hydrochloride.
Applications: Used in clinical research and pharmaceutical compounding.
Buy (1S,2S)-(+)-Pseudoephedrine (CAS No. 90-82-4)
(1S,2S)-(+)-Pseudoephedrine (CAS No. 90-82-4)
Synonyms: (+)-ψ-Ephedrine, d-Pseudoephedrine

Ephedrine

vasopressorobstetric anesthesiahypotension

Ephedrine (CAS 299-42-3) is the (1R,2S)-(−)-ephedrine enantiomer, a naturally occurring phenylpropanolamine alkaloid possessing two chiral centers and existing as one of four possible stereoisomers. This specific stereoisomer acts as a mixed-acting sympathomimetic amine, functioning both as a substrate at the norepinephrine transporter (NET) to release endogenous norepinephrine and as a direct agonist at β-adrenergic receptors.

Read more

⚠ Attention: For research use only. Not for human or veterinary use.

Molecular FormulaC10H15NO

Molecular Weight165.23 g/mol

CAS No.299-42-3

Cat. No.B3423809

Quoting multiple products?Save this product to your quote list and continue browsing.

Add to Quote List

Technical Parameters

---

Basic Identity

Product Name	Ephedrine
CAS	299-42-3
Molecular Formula	C10H15NO
Molecular Weight	165.23 g/mol

Structural Identifiers

SMILES	CC(C(C1=CC=CC=C1)O)NC
InChI	InChI=1S/C10H15NO/c1-8(11-2)10(12)9-6-4-3-5-7-9/h3-8,10-12H,1-2H3/t8-,10-/m0/s1
InChIKey	KWGRBVOPPLSCSI-WPRPVWTQSA-N

Commercial & Availability

Standard Pack Sizes	10 mg / 50 mg / 100 mg / Bulk Custom
Availability	In Stock
Custom Synthesis	Available on request

Handling Information

Solubility	In water, 56,900 mg/L at 25 °C ;  63,600 mg/L at 30 °C Soluble in oils Soluble in water, ethanol, ether, benzene and chloroform 1 g dissolves in about 20 mL water, 0.2 mL alcohol 63.6 mg/mL at 30 °C

Structure & Identifiers

---

3D Viewer

Interactive Chemical Structure Model

Ball and Stick
Sticks
Wire-Frame
Space-Filling
Show Hydrogens
Animate

+−

Ephedrine CAS 299-42-3: Stereochemically Defined Sympathomimetic Amine for Differentiated Pharmacological and Analytical Applications

---

Ephedrine (CAS 299-42-3) is the (1R,2S)-(−)-ephedrine enantiomer, a naturally occurring phenylpropanolamine alkaloid possessing two chiral centers and existing as one of four possible stereoisomers [1]. This specific stereoisomer acts as a mixed-acting sympathomimetic amine, functioning both as a substrate at the norepinephrine transporter (NET) to release endogenous norepinephrine and as a direct agonist at β-adrenergic receptors [2]. Unlike its diastereomer pseudoephedrine—which is indicated primarily as a nasal decongestant—(1R,2S)-(−)-ephedrine retains clinically meaningful direct adrenoceptor activation, measurable pressor activity, bronchodilator efficacy, and CNS stimulant properties, making stereochemical identity a critical procurement parameter [3].

1Single (1R,2S)-(−) enantiomer for stereochemistry-dependent receptor activation studies

2Mixed-acting sympathomimetic: NET substrate and direct β-adrenoceptor agonist research tool

3Differentiated from pseudoephedrine diastereomer in direct receptor activation, CNS response, and metabolic profile

View 3 References︾

Why Ephedrine (CAS 299-42-3) Cannot Be Interchanged with Pseudoephedrine or Other In-Class Alkaloids for Research and Clinical Procurement

---

Substituting ephedrine with its closest stereoisomers or N-alkyl analogs introduces quantitatively meaningful differences across every pharmacologically relevant dimension. The diastereomer pseudoephedrine—differing only in the configuration at the β-carbon—exhibits 5-fold lower pressor potency [1], approximately 2,200-fold weaker agonist activity at human β₁-adrenoceptors [2], a complete loss of direct adrenoceptor-mediated tissue response following sympathetic denervation [3], and absent CNS locomotor stimulant effects at equivalent doses [4]. Similarly, N-methylation to methylephedrine substantially increases metabolic lability, with methylephedrine undergoing extensive first-pass metabolism while ephedrine is excreted predominantly unchanged [5]. These are not marginal differences; they represent stereochemistry- and substitution-dependent switches in mechanism, potency, disposition, and target tissue selectivity that render in-class substitution scientifically invalid without explicit re-validation.

Pseudoephedrine substitution

Loss of direct β-adrenoceptor activation; markedly lower pressor response; absent CNS stimulation—stereochemistry-dependent mechanism switch may invalidate research models.

Methylephedrine substitution

Extensive N-demethylation generates ephedrine as a circulating metabolite, introducing analytical interference and confounding parent-compound quantification.

View 5 References︾

Ephedrine CAS 299-42-3: Quantitative Differential Evidence Versus Closest Analogs for Procurement Decision Support

---

Pressor Potency: Ephedrine vs. Pseudoephedrine in Canine and Human Models — 5-Fold Greater Vasopressor Efficacy

In a classic direct head-to-head comparison in anesthetized dogs, D-(−)-ephedrine (1R,2S; CAS 299-42-3) demonstrated a relative pressor potency of 100, compared to only 20 for L-(+)-pseudoephedrine, representing a 5-fold differential [1]. This animal finding is corroborated by a double-blind human volunteer study in which ephedrine 60–90 mg was sufficient to raise diastolic blood pressure above 90 mmHg, whereas pseudoephedrine required 210–240 mg to achieve the same endpoint—an approximately 3- to 4-fold potency advantage for ephedrine [2]. The quantitative pressor superiority is stereochemically determined and cannot be compensated by simple dose escalation of pseudoephedrine without introducing altered pharmacodynamic profiles.

Head-to-head

5-fold greater vasopressor response (canine); 3- to 4-fold in human volunteers

Supports model-specific vasopressor context

Canine pressor assay; double-blind human study

vasopressorobstetric anesthesiahypotensioncardiovascular pharmacology

︾

Human β-Adrenoceptor Agonist Potency: 1R,2S-Ephedrine Exhibits ~2,200-Fold Greater β₁-AR Activity than Pseudoephedrine

In cloned human β₁-adrenergic receptors expressed in Chinese hamster ovary (CHO) cells, 1R,2S-(−)-ephedrine (CAS 299-42-3) displayed an EC₅₀ of 0.5 μM with a maximal response of 68% relative to isoproterenol. By contrast, 1R,2R-(−)-pseudoephedrine required an EC₅₀ of 1,122 μM to achieve only 53% maximal response—a 2,244-fold potency difference [1]. On human β₂-AR, 1R,2S-ephedrine (EC₅₀ = 0.36 μM, 78% maximal) retained a 19-fold potency advantage over 1R,2R-pseudoephedrine (EC₅₀ = 7 μM, 50% maximal). Critically, only 1R,2S-ephedrine demonstrated measurable partial agonist activity at human β₃-AR (EC₅₀ = 45 μM, 31% maximal), while none of the other three stereoisomers showed detectable β₃-AR agonism [1]. The rank order of β₁-AR potency across the four stereoisomers was 1R,2S ≫ 1S,2R ≫ 1S,2S ≈ 1R,2R, demonstrating that both chiral centers dictate receptor activation efficacy.

Head-to-head

EC₅₀ 0.5 μM (ephedrine) vs 1,122 μM (pseudoephedrine); 2,244-fold difference

Supports receptor subtype profiling context

Cloned human β₁-AR expressed in CHO cells

beta-adrenoceptorreceptor pharmacologystructure-activity relationshipCHO cell assay

︾

Retention of Direct Adrenoceptor Activation After Sympathetic Denervation: Ephedrine vs. Pseudoephedrine

A critical mechanistic differentiation was demonstrated in rats pretreated with 6-hydroxydopamine (6-OHDA) to destroy sympathetic nerve terminals. Under these denervated conditions, the anococcygeal muscle and right atrial responses to d-pseudoephedrine were completely abolished, indicating an exclusively indirect (norepinephrine-release-dependent) mechanism. In contrast, approximately 50% of the tissue responses to l-ephedrine (CAS 299-42-3) were 6-OHDA-resistant, demonstrating a substantial direct adrenoceptor activation component [1]. This direct component was further evidenced by the finding that in human umbilical artery and vein—tissues devoid of sympathetic innervation—neither isomer produced contraction, confirming that the indirect mechanism predominates in innervated vascular beds while ephedrine uniquely retains direct activity at the tissue level [1]. The pressor response in vivo was shown to be entirely attributable to norepinephrine release from sympathetic nerves, but the dual mechanism of ephedrine provides a mechanistic rationale for its preferential use in scenarios where preserving non-innervated vascular bed flow is clinically relevant.

Head-to-head

~50% tissue response retained (ephedrine) vs 0% (pseudoephedrine) after 6-OHDA

Supports dual-mechanism interpretation

Rat anococcygeal muscle and right atrium

sympathetic denervationdirect vs indirect mechanism6-OHDAobstetric anesthesiauteroplacental blood flow

︾

CNS Locomotor Stimulation: Ephedrine Activates, Pseudoephedrine Does Not — A Qualitative Difference in Central Effects

In a direct comparative mouse study, intraperitoneal l-ephedrine (CAS 299-42-3) at 50, 100, and 200 mg/kg produced dose-dependent increases in locomotor activity, whereas d-pseudoephedrine at identical doses produced no significant increase in locomotion [1]. Furthermore, l-ephedrine shortened pentobarbital-induced sleeping time, while d-pseudoephedrine had no effect on this parameter, and l-ephedrine increased rectal temperature while d-pseudoephedrine decreased it [1]. In a broader isomer comparison using d-amphetamine as the reference standard (potency assigned = 1.0), l-ephedrine showed a central stimulant activity ratio of 24, whereas l-pseudoephedrine and d-pseudoephedrine produced measurable locomotor stimulation only at doses approaching lethal levels [2]. These findings establish that CNS stimulation is not a class property of ephedrine alkaloids; rather, it is stereospecifically conferred by the 1R,2S configuration and the S-configuration at the C-2 position.

Head-to-head

Dose-dependent locomotion for ephedrine; no significant increase for pseudoephedrine

Supports CNS-targeted study context

Mouse i.p. at 50–200 mg/kg

CNS stimulationlocomotor activitybehavioral pharmacologydrug discriminationblood-brain barrier

︾

Bronchodilator Efficacy in Human Patients: Ephedrine Produces Measurable Bronchodilation, Pseudoephedrine Does Not

In a double-blind, randomized, placebo-controlled crossover study in 12 patients with reversible airway obstruction (asthma), oral pseudoephedrine at doses of 60 mg and 180 mg produced no significant bronchodilator effect as measured by spirometry and whole-body plethysmography. Only ephedrine 25 mg (CAS 299-42-3) demonstrated a measurable bronchodilator effect, with a statistically significant percentage change in vital capacity at 2 hours post-dose compared to placebo and both pseudoephedrine doses [1]. In a separate double-blind study comparing 60 mg ephedrine versus 210 mg pseudoephedrine in patients with reversible airways obstruction, both isomers produced some bronchodilation as measured by FEV₁, but the effect of pseudoephedrine was less than half that of ephedrine despite a 3.5-fold higher dose [2]. Pseudoephedrine at single doses up to 180 mg also caused no tachycardia or hypertension, further underscoring its fundamentally different pharmacodynamic profile [1].

Head-to-head

Significant VC improvement at 25 mg ephedrine; no effect for pseudoephedrine up to 180 mg

Supports airway response research context

Double-blind crossover in reversible airway obstruction

bronchodilationasthmaFEV1reversible airway obstructionrespiratory pharmacology

︾

Metabolic Stability: Ephedrine Is Eliminated Predominantly Unchanged While Methylephedrine Is Extensively Metabolized — Implications for Analytical Reference Standard Selection

Within the ephedrine alkaloid series, the extent of metabolic transformation is directly governed by the degree of N-methyl substitution on the amino group. Under controlled acidic urine conditions in human subjects, (−)-norephedrine (zero N-methyl groups) is eliminated predominantly as unchanged drug; (−)-ephedrine (CAS 299-42-3, one N-methyl group) undergoes a small amount of N-demethylation to norephedrine but is also excreted mainly unchanged; (−)-methylephedrine (two N-methyl groups) is extensively metabolized—in part sequentially to ephedrine and then to norephedrine—with a substantially lower fraction excreted as unchanged parent compound [1]. This rank order of metabolic stability (norephedrine > ephedrine ≫ methylephedrine) means that methylephedrine generates ephedrine as a circulating metabolite, introducing analytical interference if methylephedrine is used in experiments where ephedrine is the analyte of interest. Additionally, both urinary excretion and relative metabolism of all ephedrines are pH-dependent, but the pH-sensitivity increases with successive N-methylation, giving ephedrine intermediate and more predictable renal clearance properties [1].

Class-level

Ephedrine excreted mainly unchanged; methylephedrine extensively metabolized to ephedrine

Supports bioanalytical reference standard context

Human urinary excretion under acidic pH control

pharmacokineticsmetabolic stabilityN-demethylationurinary excretionreference standard