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Record Information
Version3.6
Creation Date2006-05-18 08:27:43 UTC
Update Date2016-02-11 01:05:06 UTC
HMDB IDHMDB01920
Secondary Accession Numbers
  • HMDB14655
Metabolite Identification
Common NameDextromethorphan
DescriptionDextromethorphan is an antitussive drug that is found in many over-the-counter cold and cough preparations, usually in the form of dextromethorphan hydrobromide. Dextromethorphan is a salt of the methyl ether dextrorotatory isomer of levorphanol, a narcotic analgesic. Dextromethorphan occurs as white crystals, is sparingly soluble in water, and freely soluble in alcohol. The drug is dextrorotatory in water (at 20 degrees Celsius, Sodium D-line) with a specific rotation of +27.6 degrees. Following oral administration, dextromethorphan is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood-brain barrier. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. The first-pass through the hepatic portal vein results in some of the drug being metabolized into an active metabolite of dextromethorphan, dextrorphan, the 3-hydroxy derivative of dextromethorphan. The therapeutic activity of dextromethorphan is believed to be caused by both the drug and this metabolite. Dextromethorphan is predominantly metabolized by the liver, by various hepatic enzymes. Through various pathways, the drug undergoes (O-demethylation (which produces dextrorphan), N-demethylation, and partial conjugation with glucuronic acid and sulfate ions. The inactive metabolite (+)-3-hydroxy-N-methylmorphinan is formed as a product of DXM metabolism by these pathways. One well known metabolic catalyst involved is a specific cytochrome P450 enzyme known as 2D6, or CYP2D6. A significant portion of the population has a functional deficiency in this enzyme (and are known as poor CYP2D6 metabolizers). As CYP2D6 is the primary metabolic pathway in the inactivation of dextromethorphan, the duration of action and effects of dextromethorphan are significantly increased in such poor metabolizers. Deaths and hospitalizations have been reported in recreational use by poor CYP2D6 metabolizers. -- Wikipedia. This compound is an NMDA receptor antagonist (receptors, N-methyl-D-aspartate) and acts as a non-competitive channel blocker. It is also used to study the involvement of glutamate receptors in neurotoxicity. [PubChem]
Structure
Thumb
Synonyms
ValueSource
D-MethorphanChEBI
delta-MethorphanChEBI
DXMChEBI
δ-methorphanGenerator
Robitussin pediatric coughHMDB
TriaminicHMDB
Bayer select flu reliefHMDB
Bayer select head & chest coldHMDB
Bayer select night time coldHMDB
Benylin DMHMDB
Cerose-DMHMDB
Chloraseptic DMHMDB
Contac day & night cold/flu day capletsHMDB
Contac jr. non-drowsy formulaHMDB
Contac nighttime cold medicineHMDB
Contac severe cold formula maximum strengthHMDB
Contac severe cold formula non-drowsyHMDB
Coricidin syrupHMDB
Cough-XHMDB
D-Methorphan hydrobromideHMDB
DemorphanHMDB
Demorphan hydrobromideHMDB
DemorphineHMDB
DestrometerfanoHMDB
Dextromethorphan bromhydrateHMDB
Dextromethorphan bromideHMDB
Dextromethorphan hydrobromide monohydrateHMDB
Dextromethorphan hydrobromide oros tabletsHMDB
Dextromethorphan hydrobromideHMDB
DextrometorphanHMDB
DextromorphanHMDB
DexyromethorphanHMDB
DimacolHMDB
Dimetapp DMHMDB
Drixoral coughHMDB
Drixoral cough & congestionHMDB
Drixoral cough & sore throatHMDB
Endotussin-NNHMDB
Endotussin-NN pediatricHMDB
HoldHMDB
L-MethorphanHMDB
LevomethorphanHMDB
MethorateHMDB
Naldecon-DXHMDB
Ornex severe cold formulaHMDB
OrthoxicolHMDB
PediaCare 1HMDB
PediaCare cough-cold formulaHMDB
Prestwick_686HMDB
Robitussin CFHMDB
Robitussin cold & coughHMDB
Robitussin cough calmersHMDB
Robitussin DMHMDB
Robitussin maximum strength coughHMDB
Robitussin pediatric cough & coldHMDB
Robitussin pediatric night reliefHMDB
RomilarHMDB
Rondec DMHMDB
Ru-tuss expectorantHMDB
St. joseph cough syrupHMDB
Sudafed cough syrupHMDB
Trind-DMHMDB
Tussar DMHMDB
Tussi-organidinHMDB
Tussi-organidin DM NRHMDB
Tussi-organidin DM-S NRHMDB
Tylenol cold and flu multi-symptomHMDB
Tylenol cold and flu no drowsinessHMDB
Tylenol cold no drowsinessHMDB
Tylenol cough + decongestant liquidHMDB
Tylenol cough liquidHMDB
Tylenol flu no drowsiness gelcapsHMDB
viro-MedHMDB
Chemical FormulaC18H25NO
Average Molecular Weight271.3972
Monoisotopic Molecular Weight271.193614427
IUPAC Name(1R,9R,10R)-4-methoxy-17-methyl-17-azatetracyclo[7.5.3.0¹,¹⁰.0²,⁷]heptadeca-2(7),3,5-triene
Traditional Namelevomethorphan
CAS Registry Number125-71-3
SMILES
[H][C@]12CCCC[C@]11CCN(C)[C@H]2CC2=C1C=C(OC)C=C2
InChI Identifier
InChI=1S/C18H25NO/c1-19-10-9-18-8-4-3-5-15(18)17(19)11-13-6-7-14(20-2)12-16(13)18/h6-7,12,15,17H,3-5,8-11H2,1-2H3/t15-,17+,18+/m1/s1
InChI KeyInChIKey=MKXZASYAUGDDCJ-NJAFHUGGSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as morphinans. These are polycyclic compounds with a four-ring skeleton with three condensed six-member rings forming a partially hydrogenated phenanthrene moiety, one of which is aromatic while the two others are alicyclic.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassMorphinans
Sub ClassNot Available
Direct ParentMorphinans
Alternative Parents
Substituents
  • Morphinan
  • Benzylisoquinoline
  • Phenanthrene
  • Benzazocine
  • Tetralin
  • Anisole
  • Aralkylamine
  • Alkyl aryl ether
  • Benzenoid
  • Piperidine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
StatusDetected and Quantified
Origin
  • Drug
Biofunction
  • Analgesics, Opioid
  • Antitussive Agents
  • Excitatory Amino Acid Antagonists
Application
  • Pharmaceutical
Cellular locations
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility8.51 mg/LNot Available
LogP3.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0085 mg/mLALOGPS
logP3.75ALOGPS
logP3.49ChemAxon
logS-4.5ALOGPS
pKa (Strongest Basic)9.85ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.47 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity82.56 m3·mol-1ChemAxon
Polarizability31.74 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Membrane
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.16 +/- 0.085 uMAdult (>18 years old)Both
Peripheral Neuropathy
details
Cerebrospinal Fluid (CSF)Detected and Quantified0.435 uMChildren (1-13 years old)Not Specifiedmyoclonic seizures details
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-0.4 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0-0.2 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease References
Peripheral neuropathy
  1. Thisted RA, Klaff L, Schwartz SL, Wymer JP, Culligan NW, Gerard G, Pope LE, Berg JE: Dextromethorphan and quinidine in adult patients with uncontrolled painful diabetic peripheral neuropathy: a 29-day, multicenter, open-label, dose-escalation study. Clin Ther. 2006 Oct;28(10):1607-18. [17157116 ]
Associated OMIM IDsNone
DrugBank IDDB00514
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB022738
KNApSAcK IDNot Available
Chemspider ID4642423
KEGG Compound IDC06947
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
NuGOwiki LinkHMDB01920
Metagene LinkHMDB01920
METLIN IDNot Available
PubChem Compound5362449
PDB IDNot Available
ChEBI ID4470
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Olney JW, Labruyere J, Price MT: Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs. Science. 1989 Jun 16;244(4910):1360-2. [2660263 ]
  2. Hargreaves RJ, Hill RG, Iversen LL: Neuroprotective NMDA antagonists: the controversy over their potential for adverse effects on cortical neuronal morphology. Acta Neurochir Suppl (Wien). 1994;60:15-9. [7976530 ]
  3. Hernandez SC, Bertolino M, Xiao Y, Pringle KE, Caruso FS, Kellar KJ: Dextromethorphan and its metabolite dextrorphan block alpha3beta4 neuronal nicotinic receptors. J Pharmacol Exp Ther. 2000 Jun;293(3):962-7. [10869398 ]
  4. Brooks BR, Thisted RA, Appel SH, Bradley WG, Olney RK, Berg JE, Pope LE, Smith RA: Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a randomized trial. Neurology. 2004 Oct 26;63(8):1364-70. [15505150 ]
  5. Carliss RD, Radovsky A, Chengelis CP, O'Neill TP, Shuey DL: Oral administration of dextromethorphan does not produce neuronal vacuolation in the rat brain. Neurotoxicology. 2007 Jul;28(4):813-8. Epub 2007 Apr 6. [17573115 ]
  6. Tang YW, Rys PN, Rutledge BJ, Mitchell PS, Smith TF, Persing DH: Comparative evaluation of colorimetric microtiter plate systems for detection of herpes simplex virus in cerebrospinal fluid. J Clin Microbiol. 1998 Sep;36(9):2714-7. [9705419 ]

Enzymes

General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
General function:
Involved in ionotropic glutamate receptor activity
Specific function:
NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine. May play a role in the development of dendritic spines. May play a role in PPP2CB-NMDAR mediated signaling mechanism
Gene Name:
GRIN3A
Uniprot ID:
Q8TCU5
Molecular weight:
125464.1
General function:
Involved in C-8 sterol isomerase activity
Specific function:
Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. Involved in the regulation of different receptors it plays a role in BDNF signaling and EGF signaling. Also regulates ion channels like the potassium channel and could modulate neurotransmitter release. Plays a role in calcium signaling through modulation together with ANK2 of the ITP3R-dependent calcium efflux at the endoplasmic reticulum. Plays a role in several other cell functions including proliferation, survival and death. Originally identified for its ability to bind various psychoactive drugs it is involved in learning processes, memory and mood alteration
Gene Name:
SIGMAR1
Uniprot ID:
Q99720
Molecular weight:
25127.5
General function:
Involved in extracellular ligand-gated ion channel activity
Specific function:
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane
Gene Name:
CHRNA2
Uniprot ID:
Q15822
Molecular weight:
59764.8

Transporters

General function:
Involved in neurotransmitter:sodium symporter activity
Specific function:
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
Gene Name:
SLC6A4
Uniprot ID:
P31645
Molecular weight:
70324.165