Identification

Name
Etafedrine
Accession Number
DB11587
Type
Small Molecule
Groups
Approved
Description

Etafedrine (INN) or ethylephedrine is a long-acting bronchodilator and has been an ingredient combined with other drugs in the brand names Nethaprin [3] and Dalmacol [10]. It was previously commercially available as both the free base and as the hydrochloride salt from Sanofi-Aventis (now Sanofi) but is now no longer marketed [7].

Ethylephedrine is be formed by alkylating ephedrine with ethyl iodide. The hydrochloride is be prepared by passing hydrogen chloride through a solution of ethylephedrine in diethyl ether [11].

This belongs to the family of medications called decongestants. It acts by narrowing blood vessels in the nasal passages, helping to relieve nasal congestion [11].

Structure
Thumb
Synonyms
  • (-)-etafedrine
  • alpha-(1-(ethylmethylamino)ethyl)benzyl alcohol
Product Ingredients
IngredientUNIICASInChI Key
Etafedrine hydrochlorideY134VQ304Y530-35-8WRONACHIHQGZSD-JGAZGGJJSA-N
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
DalmacolEtafedrine hydrochloride (16.65 mg) + Doxylamine succinate (6 mg) + Ethanol (0.25 ml) + Hydrocodone bitartrate (1.65 mg) + Sodium Citrate (200 mg)SyrupOralLaboratoire Atlas Inc1983-12-31Not applicableCanada
DalmacolEtafedrine hydrochloride (16.65 mg) + Doxylamine succinate (6 mg) + Ethanol (0.25 ml) + Hydrocodone bitartrate (1.65 mg) + Sodium Citrate (200 mg)SyrupOralLaboratoire Riva Inc1997-03-26Not applicableCanada
Mercodol With DecaprynEtafedrine hydrochloride (16.65 mg) + Doxylamine succinate (6 mg) + Hydrocodone bitartrate (1.65 mg) + Sodium Citrate (200 mg)SyrupOralAventis Pharma Ltd.1994-12-312001-07-20Canada
Ratio-calmydoneEtafedrine hydrochloride (3.33 mg) + Doxylamine succinate (1.2 mg) + Hydrocodone bitartrate (0.33 mg) + Sodium Citrate (40 mg)SyrupOralTeva1981-12-312017-04-04Canada
Categories
UNII
2Y6VQU63E8
CAS number
48141-64-6
Weight
Average: 193.29
Monoisotopic: 193.146664236
Chemical Formula
C12H19NO
InChI Key
IRVLBORJKFZWMI-JQWIXIFHSA-N
InChI
InChI=1S/C12H19NO/c1-4-13(3)10(2)12(14)11-8-6-5-7-9-11/h5-10,12,14H,4H2,1-3H3/t10-,12-/m0/s1
IUPAC Name
(1R,2S)-2-[ethyl(methyl)amino]-1-phenylpropan-1-ol
SMILES
CCN(C)[C@@H](C)[C@H](O)C1=CC=CC=C1

Pharmacology

Indication

Conditions characterized by bronchial congestion and bronchospasm when an expectorant or bronchodilator action is required, such as acute bronchitis, acute episodes of chronic bronchitis and bronchial asthma [8], [9].

Associated Conditions
Pharmacodynamics

Etafedrine helps to control the cough which is associated with irritation of the mouth and throat that is not alleviated by cough medications that are less strong [7].

The results of one study in 48 individuals showed that lung FEV1 (forced expiratory volume) and lung VC (vital capacity) were significantly improved with etafedrine, sleep improved, and patients showed improved appetite in addition to the suppression of cough [3].

Mechanism of action

A sympathomimetic agent, etafedrine acts on the sympathetic receptors of the bronchial tree, relieving spasm in a manner similar to that of ephedrine [6].

Unlike ephedrine and tyramine, etafedrine does not trigger the release of epinephrine or norepinephrine, and instead acts as a selective β adrenoreceptor agonist, thereby mediating its bronchodilator effects [7].

N-ethylation of ephedrine suppresses the indirect sympathomimetic activity and markedly enhances the efficacy on beta 2- adrenoceptors [11].

TargetActionsOrganism
ABeta-2 adrenergic receptor
agonist
Human
Absorption

Similar to its parent drug, ephedrine, it is readily and completely absorbed from the gastrointestinal tract; plasma peak concentrations are reached an hour after ingestion [9].

A single oral dose of 24 mg produced an average peak plasma concentration of 0.10 mg/L [9].

Volume of distribution

Similar to ephedrine, at about 3L/kg [9].

Protein binding
Not Available
Metabolism
Not Available
Route of elimination

Excreted mainly in the urine [9].

Half life

It has a plasma half-life ranging from 3 to 6 hours depending on urinary pH [9].

Clearance
Not Available
Toxicity

This drug is a sympathomimetic, and therefore has the following adverse effects (in parallel with ephedrine) [8]: tremor, fear, anxiety, confusion, irritability, insomnia, and psychotic states. Paranoid psychosis, delusions, and hallucinations may also follow overdose [9].

The adverse effects of ephedrine and similar drugs are believed to be related to coronary artery constriction, vasospasm, shortening of cardiac refractory periods allowing re-entrant cardiac arrhythmias, hypertension-induced subarachnoid hemorrhage, cerebral artery vasoconstriction as well as sympathomimetic-induced platelet activation [8].

Affected organisms
  • Humans
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Etafedrine.
AcebutololThe therapeutic efficacy of Etafedrine can be decreased when used in combination with Acebutolol.
AcepromazineAcepromazine may decrease the vasoconstricting activities of Etafedrine.
AcetaminophenAcetaminophen may decrease the excretion rate of Etafedrine which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Etafedrine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Etafedrine which could result in a higher serum level.
Adefovir DipivoxilAdefovir Dipivoxil may decrease the excretion rate of Etafedrine which could result in a higher serum level.
AldosteroneThe risk or severity of hypokalemia can be increased when Aldosterone is combined with Etafedrine.
AlfuzosinThe therapeutic efficacy of Etafedrine can be decreased when used in combination with Alfuzosin.
AlmotriptanAlmotriptan may decrease the excretion rate of Etafedrine which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. Lindmar R, Loffelholz K, Stieh-Koch U: On the mechanism of bronchodilatation by etafedrine. Arzneimittelforschung. 1985;35(3):602-4. [PubMed:4039586]
  2. ASTROM A: Pharmacological actions of 1-N-ethyl ephedrine and 1-ephedrine; a quantitative comparison. Acta Pharmacol Toxicol (Copenh). 1948;4(1):53-64. [PubMed:18859472]
  3. Kagan G, Rose R: Double-blind trial of a long-acting bronchodilator preparation ("Nethaprin Dospan") in bronchospastic disease. Curr Med Res Opin. 1976;4(6):436-41. doi: 10.1185/03007997609112000 . [PubMed:793781]
  4. Wooltorton E, Sibbald B: Ephedra/ephedrine: cardiovascular and CNS effects. CMAJ. 2002 Mar 5;166(5):633. [PubMed:11898947]
  5. https://pubchem.ncbi.nlm.nih.gov/compound/etafedrine [Link]
  6. SA Drug label, Nethaprin [Link]
  7. Etafedrine [Link]
  8. Ephedrine [Link]
  9. Ephedrine [Link]
  10. Dalmacol [Link]
  11. Etafedrine Hydrochloride [File]
External Links
ChemSpider
85308
Wikipedia
Etafedrine
MSDS
Download (496 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SyrupOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)108-110MSDS
Predicted Properties
PropertyValueSource
Water Solubility9.44 mg/mLALOGPS
logP2.07ALOGPS
logP2.06ChemAxon
logS-1.3ALOGPS
pKa (Strongest Acidic)13.88ChemAxon
pKa (Strongest Basic)9.14ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area23.47 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity59.73 m3·mol-1ChemAxon
Polarizability22.83 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylpropanes. These are organic compounds containing a phenylpropane moiety.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenylpropanes
Direct Parent
Phenylpropanes
Alternative Parents
Aralkylamines / Trialkylamines / Secondary alcohols / 1,2-aminoalcohols / Organopnictogen compounds / Hydrocarbon derivatives / Aromatic alcohols
Substituents
Phenylpropane / Aralkylamine / 1,2-aminoalcohol / Secondary alcohol / Tertiary amine / Tertiary aliphatic amine / Organic nitrogen compound / Aromatic alcohol / Hydrocarbon derivative / Organopnictogen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Protein homodimerization activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately ...
Gene Name
ADRB2
Uniprot ID
P07550
Uniprot Name
Beta-2 adrenergic receptor
Molecular Weight
46458.32 Da
References
  1. Etafedrine [Link]
  2. Etafedrine Hydrochloride [File]

Drug created on April 27, 2016 17:42 / Updated on October 01, 2018 16:43