Identification

Name
DL-Methylephedrine
Accession Number
DB11278
Type
Small Molecule
Groups
Approved
Description

Methylephedrine is a sympathomimetic amine that appears in various over-the-counter cough and cold medications throughout the world [9], [10], [11]. The abuse of methylephedrine-containing medications has been reported in Japan. Methylephedrine is not legally available in the United States, but has been identified in cases of drug abuse [7].

Structure
Thumb
Synonyms
  • (+/-)-Methylephedrine
  • (+/-)-N-methylephedrine
  • Methylephedrine, (+/-)-
  • Methylephedrine, DL-
  • N-methylephedrine DL-form
Product Ingredients
IngredientUNIICASInChI Key
DL-Methylephedrine hydrochloride8ONA78V6FO18760-80-0NTCYWJCEOILKNG-ROLPUNSJSA-N
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Pancold SDL-Methylephedrine hydrochloride (17.5 mg/30mL) + Acetaminophen (300 mg/30mL) + Caffeine (30 mg/30mL) + Chlorphenamine (2.5 mg/30mL) + Guaifenesin (83.3 mg/30mL)LiquidOralKafus Co., Ltd2013-01-15Not applicableUs
International/Other Brands
DL-Methylephedrine HCl (Fu Yuan) / dl-Methylephedrine Hydrochloride 10% Maruishi (Maruishi Pharmaceuticals) / dl-Methylephedrine Hydrochloride 10% Metal (Nakakita Yakuhin, Japan) / dl-Methylephedrine Hydrochloride 10% Sankei (Sankei Seiyaku) / dl-Methylephedrine Hydrochloride 10% Sanwa (Sanwa Kagaku) / Methy F (Tanabe Mitsubishi Pharma) / Methylephedrine 10% Fuso (Fuso Pharmaceutical) / Methylhoedrin 10% (Mylan Seiyaku) / Tabellae DL-Methyl (Ying Yuan)
Categories
UNII
60VH42A1KJ
CAS number
1201-56-5
Weight
Average: 179.263
Monoisotopic: 179.131014171
Chemical Formula
C11H17NO
InChI Key
FMCGSUUBYTWNDP-ONGXEEELSA-N
InChI
InChI=1S/C11H17NO/c1-9(12(2)3)11(13)10-7-5-4-6-8-10/h4-9,11,13H,1-3H3/t9-,11-/m0/s1
IUPAC Name
(1R,2S)-2-(dimethylamino)-1-phenylpropan-1-ol
SMILES
C[C@@H]([C@H](O)C1=CC=CC=C1)N(C)C

Pharmacology

Indication

Used as an antitussive and decongestant [5].

Associated Conditions
Pharmacodynamics

This drugs acts as an antitussive, bronchodilator, and adrenergic receptor agonist [5]. It stimulates the alpha and beta adrenergic receptors, relieving cough and congestion [5].

As with other adrenomimetic amines, the drugs in this class are much less potent than norepinephrine itself. Members of this class of drugs increase both systolic and diastolic blood pressure, cardiac contractility, and cardiac output; in general, however, they do not increase heart rate. Bronchial smooth muscle relaxation of prolonged duration occurs, and pupils dilate [7].

Mechanism of action

The pharmacology of methylephedrine is similar to that of other members of the ephedra alkaloid class of drugs. These compounds are sympathomimetic amines because they mimic the effects of the catecholamines on the sympathetic nervous system. These alkaloids permeate the blood-brain barrier and have a direct central nervous system stimulant effect with peripheral effects; the peripheral effects are indirect and primarily mediated by norepinephrine release [7].

Methylephedrine expands the bronchia by relaxing the bronchial muscles [15].

The decrease in urination with sympathomimetic use is increased through activation of the alpha-adrenoceptors of the smooth muscles of the bladder [15].

TargetActionsOrganism
ABeta-1 adrenergic receptor
agonist
Human
AAlpha-2A adrenergic receptor
agonist
Human
AAlpha adrenergic receptor
agonist
Human
ABeta adrenergic receptor
agonist
Human
Absorption

Methylephedrine is rapidly absorbed following oral administration [7]. Peak plasma concentrations of ephedrine (from which methylephedrine is derived) occur 2-3h after administration [3]. Due to the fact that methylephedrine is a derivative of ephedrine [12], peak plasma concentrations are likely similar.

Volume of distribution

Ephedrine: 2.5-3.0 L/kg [3]. Methylephedrine is a derivative of ephedrine [12] and quickly distributed throughout the body [15].

Protein binding
Not Available
Metabolism

Methylephedrine is metabolized to give ephedrine and norephedrine [15].

Route of elimination

The primary compound excreted in urine is unchanged methylephedrine (33-40% of dose), followed by the metabolite methylephedrine-N-oxide (15% of dose), and approximately 8% of the dose excreted as ephedrine after 24 hours. About 70% of the dose is excreted in the urine as metabolites over 72 hours [7].

Alkaline urine reduces elimination to 20-35% of the dose [15].

Half life

3-6 hours (Ephedrine) [15].

Clearance
Not Available
Toxicity

Ld50 mouse (intraperitoneal): 185mg/kg [6].

Sympathomimetic drugs, such as DL-methylphedrine, can lead to an increase in catecholamines, resulting in a variety of effects [2], [13]:

Nervous System/CNS/Psychiatric

Insomnia, Headaches, Seizure, Cerebrovascular Accident, Nervousness, Tremor or other motor disturbance, Psychosis with long-term, chronic use [15]

Cardiovascular System Hypertension, Cardiac arrhythmia, Myocardial Infarction, Hypersensitivity Myocarditis

Renal System Nephrolithiasis

General Predisposition to Heat Exhaustion and Heat Stroke, Hyperglycemia, Glaucoma

The Japanese Ministry of Health made a statement in July 2017 that preparations containing this drug should not be used in children younger than 12 years old (who are highly susceptible to respiratory depression. Overseas, there have been reports that the risk of serious respiratory depression, including death, is high in children younger than 12 years old) [14].

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

Interactions

Drug Interactions
DrugInteraction
AbacavirAbacavir may decrease the excretion rate of DL-Methylephedrine which could result in a higher serum level.
AcarboseAcarbose may decrease the excretion rate of DL-Methylephedrine which could result in a higher serum level.
AcebutololThe therapeutic efficacy of DL-Methylephedrine can be decreased when used in combination with Acebutolol.
AceclofenacAceclofenac may decrease the excretion rate of DL-Methylephedrine which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of DL-Methylephedrine which could result in a higher serum level.
AcepromazineThe therapeutic efficacy of DL-Methylephedrine can be decreased when used in combination with Acepromazine.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of DL-Methylephedrine which could result in a higher serum level.
AclidiniumAclidinium may decrease the excretion rate of DL-Methylephedrine which could result in a higher serum level.
AcrivastineAcrivastine may decrease the excretion rate of DL-Methylephedrine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of DL-Methylephedrine which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. Inoue T, Suzuki S: The metabolism of (+-)-methylephedrine in rat and man. Xenobiotica. 1990 Jan;20(1):99-106. doi: 10.3109/00498259009046816. [PubMed:2327112]
  2. Dunnick JK, Kissling G, Gerken DK, Vallant MA, Nyska A: Cardiotoxicity of Ma Huang/caffeine or ephedrine/caffeine in a rodent model system. Toxicol Pathol. 2007 Aug;35(5):657-64. doi: 10.1080/01926230701459978. [PubMed:17676524]
  3. Steven B. Karch, Olaf Drummer (1996). Karch's Pathology of Drug Abuse, Third Edition. CRC Press.
  4. DL-Methylphedrine Hydrochloride [Link]
  5. Methylphedrine, DL, Drugs.com [Link]
  6. NIH Toxnet, DL Methylphedrine [Link]
  7. Methylphedrine concentrations in drug ad urine specimens [Link]
  8. Genome. JP DL-methylphedrine [Link]
  9. Daily Med, Pancold S [Link]
  10. Chlorphenamine/Dihydrocodeine/Guaifenesin/Methylephedrine/dl Uses More: https://www.ndrugs.com/?s=chlorphenamine/dihydrocodeine/guaifenesin/methylephedrine/dl More: https://www.ndrugs.com/?s=chlorphenamine/dihydrocodeine/guaifenesin/methylephedrine/dl [Link]
  11. Tossamin Plus [Link]
  12. Methylphedrine, PubChem [Link]
  13. Family Practice Notebook: Sympathomimetics [Link]
  14. Revision of Precautions Dihydrocodeine phosphate/ dl-Methylephedrine hydrochloride/ Chlorpheniramine maleate [File]
  15. 4-Methylephedrine, EUA [File]
External Links
ChemSpider
58315
ChEBI
113556
ChEMBL
CHEMBL445001
Wikipedia
Methylephedrine
MSDS
Download (68.6 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)208MSDS
boiling point (°C)251.3https://www.chemsrc.com/en/cas/18760-80-0_1189835.html
logP2.47https://www.chemsrc.com/en/cas/18760-80-0_1189835.html
Predicted Properties
PropertyValueSource
Water Solubility15.4 mg/mLALOGPS
logP1.73ALOGPS
logP1.7ChemAxon
logS-1.1ALOGPS
pKa (Strongest Acidic)13.88ChemAxon
pKa (Strongest Basic)8.86ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area23.47 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity54.98 m3·mol-1ChemAxon
Polarizability20.55 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 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
Receptor signaling protein activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately e...
Gene Name
ADRB1
Uniprot ID
P08588
Uniprot Name
Beta-1 adrenergic receptor
Molecular Weight
51322.1 Da
References
  1. Genome. JP DL-methylphedrine [Link]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
Molecular Weight
48956.275 Da
References
  1. Genome. JP DL-methylphedrine [Link]
Kind
Protein group
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...

Components:
References
  1. Genome. JP DL-methylphedrine [Link]
Kind
Protein group
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Receptor signaling protein activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately e...

Components:
References
  1. Genome. JP DL-methylphedrine [Link]

Drug created on December 03, 2015 09:52 / Updated on November 02, 2018 08:53