U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C18H25NO
Molecular Weight 271.3972
Optical Activity ( + )
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Dextromethorphan

SMILES

[H][C@]12CCCC[C@]13CCN(C)[C@H]2CC4=CC=C(OC)C=C34

InChI

InChIKey=MKXZASYAUGDDCJ-NJAFHUGGSA-N
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

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/2694543 http://www.who.int/medicines/areas/quality_safety/5.1Dextromethorphan_pre-review.pdf http://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21620_mucinex_lbl.pdf https://www.ncbi.nlm.nih.gov/pubmed/25420446

Dextromethorphan is a non-narcotic morphine derivative widely used as an antitussive for almost 40 years. It has attracted attention due to its anticonvulsant and neuroprotective properties. It is a cough suppressant in many over-the-counter cold and cough medicines. In 2010, the FDA approved the combination product dextromethorphan/quinidine for the treatment of pseudobulbar affect. Dextromethorphan suppresses the cough reflex by a direct action on the cough center in the medulla of the brain. Dextromethorphan shows high-affinity binding to several regions of the brain, including the medullary cough center. This compound is an NMDA receptor antagonist and acts as a non-competitive channel blocker. It is one of the widely used antitussives and is used to study the involvement of glutamate receptors in neurotoxicity. Dextromethorphan (DM) is a sigma-1 receptor agonist and an uncompetitive NMDA receptor antagonist. The mechanism by which dextromethorphan exerts therapeutic effects in patients with pseudobulbar affect is unknown. Dextromethorphan should not be taken with monoamine oxidase inhibitors due to the potential for serotonin syndrome. Dextromethorphan is extensively metabolized by CYP2D6 to dextrorphan, which is rapidly glucuronidated and unable to cross the blood-brain barrier.

Originator

Curator's Comment: # in a Swiss and US patent application from Hoffmann-La Roche in 1946 and 1947, respectively

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
205.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
MUCINEX DM

Approved Use

Helps loosen phlegm (mucus) and thin bronchial secretions to rid the bronchial passageways of bothersome mucus and make coughs more productive: temporarily relieves: cough due to minor throat and bronchial irritation as may occur with the common cold or inhaled irritants; the intensity of coughing; the impulse to cough to help you get to sleep

Launch Date

2004
Primary
NUEDEXTA

Approved Use

NUEDEXTA is indicated for the treatment of pseudobulbar affect (PBA). PBA occurs secondary to a variety of otherwise unrelated neurologic conditions, and is characterized by involuntary, sudden, and frequent episodes of laughing and/or crying. PBA episodes typically occur out of proportion or incongruent to the underlying emotional state. PBA is a specific condition, distinct from other types of emotional lability that may occur in patients with neurological disease or injury.

Launch Date

2010
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
4.2 ng/mL
45 mg 2 times / day steady-state, oral
dose: 45 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DEXTROMETHORPHAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
7.7 ng/mL
60 mg 2 times / day steady-state, oral
dose: 60 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DEXTROMETHORPHAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
95.5 ng/mL
30 mg 2 times / day steady-state, oral
dose: 30 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: QUINIDINE
DEXTROMETHORPHAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
15.9 ng/mL
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered: QUINIDINE
DEXTROMETHORPHAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2.9 ng/mL
30 mg 2 times / day steady-state, oral
dose: 30 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DEXTROMETHORPHAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
123.5 ng/mL
30 mg 2 times / day steady-state, oral
dose: 30 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: QUINIDINE
DEXTRORPHAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
124.9 ng/mL
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered: QUINIDINE
DEXTRORPHAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
599 ng/mL
45 mg 2 times / day steady-state, oral
dose: 45 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DEXTRORPHAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
709 ng/mL
60 mg 2 times / day steady-state, oral
dose: 60 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DEXTRORPHAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
32 ng × h/mL
45 mg 2 times / day steady-state, oral
dose: 45 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DEXTROMETHORPHAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
52 ng × h/mL
60 mg 2 times / day steady-state, oral
dose: 60 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DEXTROMETHORPHAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1049 ng × h/mL
30 mg 2 times / day steady-state, oral
dose: 30 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: QUINIDINE
DEXTROMETHORPHAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
133.3 ng × h/mL
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered: QUINIDINE
DEXTROMETHORPHAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
17.8 ng × h/mL
30 mg 2 times / day steady-state, oral
dose: 30 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DEXTROMETHORPHAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1000.5 ng × h/mL
30 mg 2 times / day steady-state, oral
dose: 30 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: QUINIDINE
DEXTRORPHAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
933.8 ng × h/mL
30 mg single, oral
dose: 30 mg
route of administration: Oral
experiment type: SINGLE
co-administered: QUINIDINE
DEXTRORPHAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2898 ng × h/mL
45 mg 2 times / day steady-state, oral
dose: 45 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DEXTRORPHAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
3608 ng × h/mL
60 mg 2 times / day steady-state, oral
dose: 60 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DEXTRORPHAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
68 nM*h
30 mg single, oral
dose: 30 mg
route of administration: oral
experiment type: single
co-administered:
DEXTROMETHORPHAN plasma
Homo sapiens
population: healthy
age: adults
sex:
food status:
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
13.1 h
30 mg 2 times / day steady-state, oral
dose: 30 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: QUINIDINE
DEXTROMETHORPHAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
50 mg 4 times / day steady, oral
Dose: 50 mg, 4 times / day
Route: oral
Route: steady
Dose: 50 mg, 4 times / day
Sources:
unhealthy, 19-52 years
n = 16
Health Status: unhealthy
Condition: chronic intractable partial onset seizures
Age Group: 19-52 years
Sex: M+F
Population Size: 16
Sources:
960 mg 1 times / day multiple, oral
Highest studied dose
Dose: 960 mg, 1 times / day
Route: oral
Route: multiple
Dose: 960 mg, 1 times / day
Sources:
unhealthy, 19-67 years
n = 11
Health Status: unhealthy
Condition: Huntington's disease
Age Group: 19-67 years
Sex: M+F
Population Size: 11
Sources:
120 mg single, oral
Recommended
Dose: 120 mg
Route: oral
Route: single
Dose: 120 mg
Sources:
healthy, 26.5 years
n = 40
Health Status: healthy
Age Group: 26.5 years
Sex: M+F
Population Size: 40
Sources:
900 mg single, oral
Overdose
Dose: 900 mg
Route: oral
Route: single
Dose: 900 mg
Sources:
unknown, 27 years
n = 1
Health Status: unknown
Age Group: 27 years
Sex: M
Population Size: 1
Sources:
Other AEs: Ischemic colitis...
Other AEs:
Ischemic colitis (1 patient)
Sources:
270 mg single, oral
Overdose
Dose: 270 mg
Route: oral
Route: single
Dose: 270 mg
Sources:
unknown, 3 years
n = 1
Health Status: unknown
Age Group: 3 years
Sex: M
Population Size: 1
Sources:
Other AEs: Lethargy, Ataxia...
Other AEs:
Lethargy (1 patient)
Ataxia (1 patient)
Nystagmus (1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Ischemic colitis 1 patient
900 mg single, oral
Overdose
Dose: 900 mg
Route: oral
Route: single
Dose: 900 mg
Sources:
unknown, 27 years
n = 1
Health Status: unknown
Age Group: 27 years
Sex: M
Population Size: 1
Sources:
Ataxia 1 patient
270 mg single, oral
Overdose
Dose: 270 mg
Route: oral
Route: single
Dose: 270 mg
Sources:
unknown, 3 years
n = 1
Health Status: unknown
Age Group: 3 years
Sex: M
Population Size: 1
Sources:
Lethargy 1 patient
270 mg single, oral
Overdose
Dose: 270 mg
Route: oral
Route: single
Dose: 270 mg
Sources:
unknown, 3 years
n = 1
Health Status: unknown
Age Group: 3 years
Sex: M
Population Size: 1
Sources:
Nystagmus 1 patient
270 mg single, oral
Overdose
Dose: 270 mg
Route: oral
Route: single
Dose: 270 mg
Sources:
unknown, 3 years
n = 1
Health Status: unknown
Age Group: 3 years
Sex: M
Population Size: 1
Sources:
Overview

OverviewOther

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
The need for rational therapeutics in the use of cough and cold medicine in infants.
1992 Apr
Modification of naloxone-induced withdrawal signs by dextromethorphan in morphine-dependent mice.
1999 Jul 14
Gamma-aminobutyric acid and glutamic acid receptors may mediate theophylline-induced seizures in mice.
1999 Mar
[Acute cholestatic hepatitis induced by dextromethorphan].
1999 Oct
Mimicking gene defects to treat drug dependence.
2000
Dextromethorphan and its metabolite dextrorphan block alpha3beta4 neuronal nicotinic receptors.
2000 Jun
Cytochrome P450 2D6.1 and cytochrome P450 2D6.10 differ in catalytic activity for multiple substrates.
2001 Aug
Evaluation of cytochrome P450 probe substrates commonly used by the pharmaceutical industry to study in vitro drug interactions.
2002 Dec
Bridging sectors. Medicon Valley.
2002 Dec 12
Biotechnology in the Medicon Valley.
2002 May
Dextromethorphan and memantine in painful diabetic neuropathy and postherpetic neuralgia: efficacy and dose-response trials.
2002 May
Non-competitive NMDA receptor antagonists moderate seizure-induced c-fos expression in the rat cerebral cortex.
2003 Feb 15
Total and corrected antioxidant capacity in hemodialyzed patients.
2003 Jul 1
mRNA and protein expression of dog liver cytochromes P450 in relation to the metabolism of human CYP2C substrates.
2003 Mar
Analysis of pharmacokinetic parameters for assessment of dextromethorphan metabolic phenotypes.
2003 Sep-Oct
Effect of St John's wort on the activities of CYP1A2, CYP3A4, CYP2D6, N-acetyltransferase 2, and xanthine oxidase in healthy males and females.
2004 Apr
Evidence of significant contribution from CYP3A5 to hepatic drug metabolism.
2004 Dec
Effect of dextromethorphan, diphenhydramine, and placebo on nocturnal cough and sleep quality for coughing children and their parents.
2004 Jul
Potential of pranlukast and zafirlukast in the inhibition of human liver cytochrome P450 enzymes.
2004 May
Bladder emptying over a period of 10-45 years after a traumatic spinal cord injury.
2004 Nov
Treatment of pseudobulbar affect in ALS with dextromethorphan/quinidine: a randomized trial.
2004 Oct 26
[Dextromethorphan enhances analgesic activity of propacetamol--experimental study].
2005
Epigenetic silencing of DSC3 is a common event in human breast cancer.
2005
High-throughput screening of inhibitory potential of nine cytochrome P450 enzymes in vitro using liquid chromatography/tandem mass spectrometry.
2005
Dextromethorphan psychosis, dependence and physical withdrawal.
2005 Dec
Effect of dextrometorphan and dextrorphan on nicotine and neuronal nicotinic receptors: in vitro and in vivo selectivity.
2005 Feb
Inhibitory effects of nicardipine to cytochrome P450 (CYP) in human liver microsomes.
2005 May
Recombinant production of human microsomal cytochrome P450 2D6 in the methylotrophic yeast Pichia pastoris.
2005 Nov
Cluster formation as a tool for development in Medicon Valley.
2006 Jan-Feb
Mesenteric artery clamping/unclamping-induced acute lung injury is attenuated by N-methyl-D-aspartate antagonist dextromethorphan.
2006 Nov-Dec
Immunohistological assessment of the synovial tissue in small joints in rheumatoid arthritis: validation of a minimally invasive ultrasound-guided synovial biopsy procedure.
2007
Cough mixture abuse as a novel cause of folate deficiency: a prospective, community-based, controlled study.
2007 Apr
Effects of dextromethorphan on dopamine dependent behaviours in rats.
2007 Aug
Treatment of the common cold.
2007 Feb 15
A placebo double-blind pilot study of dextromethorphan for problematic behaviors in children with autism.
2007 Jan
In vitro interaction cocktail assay for nine major cytochrome P450 enzymes with 13 probe reactions and a single LC/MSMS run: analytical validation and testing with monoclonal anti-CYP antibodies.
2007 Jul
Prior exposure to uninfected mosquitoes enhances mortality in naturally-transmitted West Nile virus infection.
2007 Nov 14
Ubiquitous computing for remote cardiac patient monitoring: a survey.
2008
Mechanical aspects of a multidirectional, angular stable osteosynthesis system and comparison with four conventional systems.
2008 Apr
Effects of common antitussive drugs on the hERG potassium channel current.
2008 Dec
Anti-inflammatory effects of dimemorfan on inflammatory cells and LPS-induced endotoxin shock in mice.
2008 Jul
Functional expression and comparative characterization of nine murine cytochromes P450 by fluorescent inhibition screening.
2008 Jul
Effect of fenofibrate on microcirculation and wound healing in healthy and diabetic mice.
2009
Dextromethorphan reduces oxidative stress and inhibits atherosclerosis and neointima formation in mice.
2009 Apr 1
The diagnostic role of glycosaminoglycans in pleural effusions: a pilot study.
2009 Feb 18
Amyotrophic lateral sclerosis.
2009 Feb 3
Characterization of retrieved orthodontic miniscrew implants.
2009 Jan
Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: the NNIPPS study.
2009 Jan
Retrospective analysis of titanium plate-retained prostheses placed after total rhinectomy.
2009 Jan-Feb
[Bone anchored hearing aids (BAHA)].
2009 Mar
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: https://www.ncbi.nlm.nih.gov/pubmed/1503667 https://www.ncbi.nlm.nih.gov/pubmed/26000221
15-30 mg 3 to 4 times per day (cough) 20-30 mg twice daily (pseudobulbar affect)
Route of Administration: Oral
In vitro studies pre- and immature oligodendroglial (OLN-93) cells were subjected to hyperoxic conditions for 48 h after pre-treatment with increasing doses of dextromethorphan.
Name Type Language
Dextromethorphan
HSDB   INN   MART.   MI   USP   USP-RS   VANDF   WHO-DD  
INN  
Official Name English
BA-2666
Code English
BA 2666
Common Name English
DEX
Common Name English
NSC-751452
Code English
DEXTROMETHORPHAN [VANDF]
Common Name English
Dextromethorphan [WHO-DD]
Common Name English
NODEX
Common Name English
DEXTROMETHORPHAN [MI]
Common Name English
D-METHORPHAN
Common Name English
(+)-DEXTROMETHORPHAN
Common Name English
DXM
Common Name English
DEXTROMETHORPHAN [USP MONOGRAPH]
Common Name English
DEXTROMETHORPHAN [MART.]
Common Name English
MORPHINAN, 3-METHOXY-17-METHYL-, (9.ALPHA.,13.ALPHA.,14.ALPHA.)-
Common Name English
3-Methoxy-17-methyl-9α,13α,14α-morphinan
Common Name English
DEXTROMETHORPHAN [HSDB]
Common Name English
dextromethorphan [INN]
Common Name English
DEXTROMETHORPHAN [USP-RS]
Common Name English
Classification Tree Code System Code
NDF-RT N0000181821
Created by admin on Fri Dec 15 15:04:42 GMT 2023 , Edited by admin on Fri Dec 15 15:04:42 GMT 2023
CFR 21 CFR 341.14
Created by admin on Fri Dec 15 15:04:42 GMT 2023 , Edited by admin on Fri Dec 15 15:04:42 GMT 2023
CFR 21 CFR 341.74
Created by admin on Fri Dec 15 15:04:42 GMT 2023 , Edited by admin on Fri Dec 15 15:04:42 GMT 2023
WHO-VATC QN07XX59
Created by admin on Fri Dec 15 15:04:42 GMT 2023 , Edited by admin on Fri Dec 15 15:04:42 GMT 2023
WHO-VATC QR05DA09
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WHO-ATC R05DA09
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NDF-RT N0000182149
Created by admin on Fri Dec 15 15:04:42 GMT 2023 , Edited by admin on Fri Dec 15 15:04:42 GMT 2023
WHO-ATC N07XX59
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NCI_THESAURUS C2199
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Code System Code Type Description
RS_ITEM_NUM
1180503
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PRIMARY
NCI_THESAURUS
C62022
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PRIMARY
NSC
751452
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PRIMARY
MERCK INDEX
m4227
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PRIMARY Merck Index
INN
166
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PRIMARY
NDF-RT
N0000181819
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PRIMARY Uncompetitive NMDA Receptor Antagonists [MoA]
CHEBI
4470
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PRIMARY
EPA CompTox
DTXSID3022908
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PRIMARY
HSDB
3056
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PRIMARY
CAS
125-71-3
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PRIMARY
EVMPD
SUB07051MIG
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PRIMARY
ECHA (EC/EINECS)
204-752-2
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PRIMARY
ChEMBL
CHEMBL52440
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PRIMARY
NDF-RT
N0000182147
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PRIMARY Sigma-1 Receptor Agonists [MoA]
DRUG CENTRAL
842
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PRIMARY
DRUG BANK
DB00514
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PRIMARY
IUPHAR
6953
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PRIMARY
FDA UNII
7355X3ROTS
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PRIMARY
LACTMED
Dextromethorphan
Created by admin on Fri Dec 15 15:04:42 GMT 2023 , Edited by admin on Fri Dec 15 15:04:42 GMT 2023
PRIMARY
DAILYMED
7355X3ROTS
Created by admin on Fri Dec 15 15:04:42 GMT 2023 , Edited by admin on Fri Dec 15 15:04:42 GMT 2023
PRIMARY
RXCUI
3289
Created by admin on Fri Dec 15 15:04:42 GMT 2023 , Edited by admin on Fri Dec 15 15:04:42 GMT 2023
ALTERNATIVE RxNorm
WIKIPEDIA
DEXTROMETHORPHAN
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PRIMARY
SMS_ID
100000092321
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PRIMARY
MESH
D003915
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PRIMARY
PUBCHEM
5360696
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PRIMARY
RXCUI
236146
Created by admin on Fri Dec 15 15:04:42 GMT 2023 , Edited by admin on Fri Dec 15 15:04:42 GMT 2023
PRIMARY