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 Riva Inc1997-03-26Not applicableCanada
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
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].

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
DrugInteractionDrug group
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.Experimental
AcepromazineAcepromazine may decrease the vasoconstricting activities of Etafedrine.Approved, Vet Approved
AlfuzosinAlfuzosin may decrease the vasoconstricting activities of Etafedrine.Approved, Investigational
AmphetamineThe risk or severity of adverse effects can be increased when Amphetamine is combined with Etafedrine.Approved, Illicit, Investigational
AripiprazoleAripiprazole may decrease the vasoconstricting activities of Etafedrine.Approved, Investigational
AsenapineAsenapine may decrease the vasoconstricting activities of Etafedrine.Approved
AtomoxetineAtomoxetine may increase the tachycardic activities of Etafedrine.Approved
AtosibanThe risk or severity of adverse effects can be increased when Etafedrine is combined with Atosiban.Approved, Investigational
AzosemideEtafedrine may increase the hypokalemic activities of Azosemide.Investigational
BendroflumethiazideEtafedrine may increase the hypokalemic activities of Bendroflumethiazide.Approved
BenmoxinThe risk or severity of adverse effects can be increased when Benmoxin is combined with Etafedrine.Withdrawn
BenzthiazideEtafedrine may increase the hypokalemic activities of Benzthiazide.Approved
BetahistineThe therapeutic efficacy of Etafedrine can be decreased when used in combination with Betahistine.Approved, Investigational
BrexpiprazoleBrexpiprazole may decrease the vasoconstricting activities of Etafedrine.Approved, Investigational
BrofaromineThe risk or severity of adverse effects can be increased when Brofaromine is combined with Etafedrine.Experimental
BumetanideEtafedrine may increase the hypokalemic activities of Bumetanide.Approved
BunazosinBunazosin may decrease the vasoconstricting activities of Etafedrine.Investigational
CaroxazoneThe risk or severity of adverse effects can be increased when Caroxazone is combined with Etafedrine.Withdrawn
ChlorothiazideEtafedrine may increase the hypokalemic activities of Chlorothiazide.Approved, Vet Approved
ChlorpromazineChlorpromazine may decrease the vasoconstricting activities of Etafedrine.Approved, Investigational, Vet Approved
ChlorthalidoneEtafedrine may increase the hypokalemic activities of Chlorthalidone.Approved
ClozapineClozapine may decrease the vasoconstricting activities of Etafedrine.Approved
CyclopenthiazideEtafedrine may increase the hypokalemic activities of Cyclopenthiazide.Experimental
DapiprazoleDapiprazole may decrease the vasoconstricting activities of Etafedrine.Approved
DextroamphetamineDextroamphetamine may decrease the vasoconstricting activities of Etafedrine.Approved, Illicit
DoxazosinDoxazosin may decrease the vasoconstricting activities of Etafedrine.Approved
DronedaroneDronedarone may decrease the vasoconstricting activities of Etafedrine.Approved
DroperidolDroperidol may decrease the vasoconstricting activities of Etafedrine.Approved, Vet Approved
EpinephrineEpinephrine may decrease the vasoconstricting activities of Etafedrine.Approved, Vet Approved
EpitizideEtafedrine may increase the hypokalemic activities of Epitizide.Experimental
EscitalopramEscitalopram may decrease the vasoconstricting activities of Etafedrine.Approved, Investigational
Etacrynic acidEtafedrine may increase the hypokalemic activities of Etacrynic acid.Approved, Investigational
FlupentixolFlupentixol may decrease the vasoconstricting activities of Etafedrine.Approved, Investigational, Withdrawn
FurazolidoneThe risk or severity of adverse effects can be increased when Furazolidone is combined with Etafedrine.Approved, Investigational, Vet Approved
FurosemideEtafedrine may increase the hypokalemic activities of Furosemide.Approved, Vet Approved
HarmalineThe risk or severity of adverse effects can be increased when Harmaline is combined with Etafedrine.Experimental
HydracarbazineThe risk or severity of adverse effects can be increased when Hydracarbazine is combined with Etafedrine.Experimental
HydrochlorothiazideEtafedrine may increase the hypokalemic activities of Hydrochlorothiazide.Approved, Vet Approved
HydroflumethiazideEtafedrine may increase the hypokalemic activities of Hydroflumethiazide.Approved, Investigational
IloperidoneIloperidone may decrease the vasoconstricting activities of Etafedrine.Approved
IndapamideEtafedrine may increase the hypokalemic activities of Indapamide.Approved
IndoraminIndoramin may decrease the vasoconstricting activities of Etafedrine.Withdrawn
IproclozideThe risk or severity of adverse effects can be increased when Iproclozide is combined with Etafedrine.Withdrawn
IproniazidThe risk or severity of adverse effects can be increased when Iproniazid is combined with Etafedrine.Withdrawn
IsocarboxazidThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Etafedrine.Approved
LisdexamfetamineLisdexamfetamine may decrease the vasoconstricting activities of Etafedrine.Approved, Investigational
MebanazineThe risk or severity of adverse effects can be increased when Mebanazine is combined with Etafedrine.Withdrawn
MethotrimeprazineMethotrimeprazine may decrease the vasoconstricting activities of Etafedrine.Approved, Investigational
MethyclothiazideEtafedrine may increase the hypokalemic activities of Methyclothiazide.Approved
Methylene blueThe risk or severity of adverse effects can be increased when Methylene blue is combined with Etafedrine.Approved, Investigational
MetolazoneEtafedrine may increase the hypokalemic activities of Metolazone.Approved
MinaprineThe risk or severity of adverse effects can be increased when Minaprine is combined with Etafedrine.Approved
MoclobemideThe risk or severity of adverse effects can be increased when Moclobemide is combined with Etafedrine.Approved, Investigational
NefazodoneNefazodone may decrease the vasoconstricting activities of Etafedrine.Approved, Withdrawn
NialamideThe risk or severity of adverse effects can be increased when Nialamide is combined with Etafedrine.Withdrawn
NicardipineNicardipine may decrease the vasoconstricting activities of Etafedrine.Approved, Investigational
NiguldipineNiguldipine may decrease the vasoconstricting activities of Etafedrine.Experimental
OctamoxinThe risk or severity of adverse effects can be increased when Octamoxin is combined with Etafedrine.Withdrawn
OlanzapineOlanzapine may decrease the vasoconstricting activities of Etafedrine.Approved, Investigational
PaliperidonePaliperidone may decrease the vasoconstricting activities of Etafedrine.Approved
PargylineThe risk or severity of adverse effects can be increased when Pargyline is combined with Etafedrine.Approved
PhenelzineThe risk or severity of adverse effects can be increased when Phenelzine is combined with Etafedrine.Approved
PheniprazineThe risk or severity of adverse effects can be increased when Pheniprazine is combined with Etafedrine.Withdrawn
PhenoxybenzaminePhenoxybenzamine may decrease the vasoconstricting activities of Etafedrine.Approved
PhenoxypropazineThe risk or severity of adverse effects can be increased when Phenoxypropazine is combined with Etafedrine.Withdrawn
PhentolaminePhentolamine may decrease the vasoconstricting activities of Etafedrine.Approved
PiretanideEtafedrine may increase the hypokalemic activities of Piretanide.Approved
PirlindoleThe risk or severity of adverse effects can be increased when Pirlindole is combined with Etafedrine.Approved
PivhydrazineThe risk or severity of adverse effects can be increased when Pivhydrazine is combined with Etafedrine.Withdrawn
PizotifenPizotifen may decrease the vasoconstricting activities of Etafedrine.Approved
PolythiazideEtafedrine may increase the hypokalemic activities of Polythiazide.Approved
PrazosinPrazosin may decrease the vasoconstricting activities of Etafedrine.Approved
ProcaineThe risk or severity of adverse effects can be increased when Procaine is combined with Etafedrine.Approved, Investigational, Vet Approved
ProcarbazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Etafedrine.Approved, Investigational
PromazinePromazine may decrease the vasoconstricting activities of Etafedrine.Approved, Vet Approved
PropericiazinePropericiazine may decrease the vasoconstricting activities of Etafedrine.Approved, Investigational
PropiomazinePropiomazine may decrease the vasoconstricting activities of Etafedrine.Approved
PropiverinePropiverine may decrease the vasoconstricting activities of Etafedrine.Approved, Investigational
QuetiapineQuetiapine may decrease the vasoconstricting activities of Etafedrine.Approved
QuinethazoneEtafedrine may increase the hypokalemic activities of Quinethazone.Approved
QuinidineQuinidine may decrease the vasoconstricting activities of Etafedrine.Approved, Investigational
RacepinephrineRacepinephrine may decrease the vasoconstricting activities of Etafedrine.Approved
RasagilineThe risk or severity of adverse effects can be increased when Rasagiline is combined with Etafedrine.Approved
RisperidoneRisperidone may decrease the vasoconstricting activities of Etafedrine.Approved, Investigational
SafrazineThe risk or severity of adverse effects can be increased when Safrazine is combined with Etafedrine.Withdrawn
SelegilineThe risk or severity of adverse effects can be increased when Selegiline is combined with Etafedrine.Approved, Investigational, Vet Approved
SilodosinSilodosin may decrease the vasoconstricting activities of Etafedrine.Approved
SpironolactoneSpironolactone may decrease the vasoconstricting activities of Etafedrine.Approved
TamsulosinTamsulosin may decrease the vasoconstricting activities of Etafedrine.Approved, Investigational
TerazosinTerazosin may decrease the vasoconstricting activities of Etafedrine.Approved
ThioproperazineThioproperazine may decrease the vasoconstricting activities of Etafedrine.Approved
ThioridazineThioridazine may decrease the vasoconstricting activities of Etafedrine.Approved, Withdrawn
TolazolineTolazoline may decrease the vasoconstricting activities of Etafedrine.Approved, Vet Approved
ToloxatoneThe risk or severity of adverse effects can be increased when Toloxatone is combined with Etafedrine.Approved
TorasemideEtafedrine may increase the hypokalemic activities of Torasemide.Approved
TranylcypromineThe risk or severity of adverse effects can be increased when Tranylcypromine is combined with Etafedrine.Approved, Investigational
TrazodoneTrazodone may decrease the vasoconstricting activities of Etafedrine.Approved, Investigational
TrichlormethiazideEtafedrine may increase the hypokalemic activities of Trichlormethiazide.Approved, Vet Approved
TrifluoperazineTrifluoperazine may decrease the vasoconstricting activities of Etafedrine.Approved, Investigational
TrimazosinTrimazosin may decrease the vasoconstricting activities of Etafedrine.Experimental
UrapidilUrapidil may decrease the vasoconstricting activities of Etafedrine.Investigational
VerapamilVerapamil may decrease the vasoconstricting activities of Etafedrine.Approved
ZiprasidoneZiprasidone may decrease the vasoconstricting activities of Etafedrine.Approved
ZuclopenthixolZuclopenthixol may decrease the vasoconstricting activities of Etafedrine.Approved, Investigational
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 June 02, 2018 09:43