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

Details

Stereochemistry ABSOLUTE
Molecular Formula C18H25NO.HI
Molecular Weight 399.3103
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DEXTROMETHORPHAN HYDRIODIDE

SMILES

CN1CC[C@]23CCCC[C@]3([H])[C@]1([H])Cc4ccc(cc42)OC.I

InChI

InChIKey=RWSHVMCJJPXQSP-URVXVIKDSA-N
InChI=1S/C18H25NO.HI/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;1H/t15-,17+,18+;/m1./s1

HIDE SMILES / InChI

Molecular Formula HI
Molecular Weight 127.9124
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C18H25NO
Molecular Weight 271.3979
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

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

1.08319677E12
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

1.28580479E12
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
Differential effects of morphinan drugs on haloperidol-induced catalepsy in rats: a comparative study with an N-methyl-D-aspartate antagonist.
1991 Mar-Apr
The need for rational therapeutics in the use of cough and cold medicine in infants.
1992 Apr
Expression, purification, biochemical characterization, and comparative function of human cytochrome P450 2D6.1, 2D6.2, 2D6.10, and 2D6.17 allelic isoforms.
2002 Dec
Bridging sectors. Medicon Valley.
2002 Dec 12
Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain.
2003 Dec 9
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
Analgesic effect of dextromethorphan in neuropathic pain.
2004 Mar
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
Phenotypical expression of CYP2D6 in amerindians of tepehuano origin from Durango, Mexico.
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
The dextromethorphan analog dimemorfan attenuates kainate-induced seizures via sigma1 receptor activation: comparison with the effects of dextromethorphan.
2005 Apr
Characterization of microsomal cytochrome P450-dependent monooxygenases in the rat olfactory mucosa.
2005 Aug
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
Multiple P450 substrates in a single run: rapid and comprehensive in vitro interaction assay.
2005 Jan
MK-801 and dextromethorphan block microglial activation and protect against methamphetamine-induced neurotoxicity.
2005 Jul 19
Evaluation of dextromethorphan metabolism using hepatocytes from CYP2D6 poor and extensive metabolizers.
2005 Jun
Cytochrome P450 2D6 (CYP2D6) inhibitory constituents of Catharanthus roseus.
2005 Jun
Dextromethorphan-induced delirium and possible methadone interaction.
2005 Mar
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
Side effects of dextromethorphan abuse, a case series.
2005 Sep
Cluster formation as a tool for development in Medicon Valley.
2006 Jan-Feb
Dextromethorphan-induced neurologic illness in a patient with negative toxicology findings.
2006 Jun 27
Randomized, controlled trial of dextromethorphan/quinidine for pseudobulbar affect in multiple sclerosis.
2006 May
Mesenteric artery clamping/unclamping-induced acute lung injury is attenuated by N-methyl-D-aspartate antagonist dextromethorphan.
2006 Nov-Dec
Co-administration of dextromethorphan with methamphetamine attenuates methamphetamine-induced rewarding and behavioral sensitization.
2006 Sep
Immunohistological assessment of the synovial tissue in small joints in rheumatoid arthritis: validation of a minimally invasive ultrasound-guided synovial biopsy procedure.
2007
Sex differences in the potency of kappa opioids and mixed-action opioids administered systemically and at the site of inflammation against capsaicin-induced hyperalgesia in rats.
2007 Apr
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
Free energies of binding of R- and S-propranolol to wild-type and F483A mutant cytochrome P450 2D6 from molecular dynamics simulations.
2007 Jul
Validated method for rapid inhibition screening of six cytochrome P450 enzymes by liquid chromatography-tandem mass spectrometry.
2007 Jun 1
Development and full validation of six inhibition assays for five major cytochrome P450 enzymes in human liver microsomes using an automated 96-well microplate incubation format and LC-MS/MS analysis.
2007 May 9
Effect of sodium ozagrel on the activity of rat CYP2D6.
2007 Nov 14
Dextromethorphan: a review of N-methyl-d-aspartate receptor antagonist in the management of pain.
2007 Spring
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
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.
Substance Class Chemical
Created
by admin
on Sat Jun 26 03:46:15 UTC 2021
Edited
by admin
on Sat Jun 26 03:46:15 UTC 2021
Record UNII
086F8ZEM77
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DEXTROMETHORPHAN HYDRIODIDE
Common Name English
MORPHINAN, 3-METHOXY-17-METHYL-, HYDRIODIDE, (9.ALPHA.,13.ALPHA.,14.ALPHA.)-
Common Name English
DEXTROMETHORPHAN HYDROIODIDE
Common Name English
Code System Code Type Description
DRUG BANK
DBSALT001897
Created by admin on Sat Jun 26 03:46:15 UTC 2021 , Edited by admin on Sat Jun 26 03:46:15 UTC 2021
PRIMARY
FDA UNII
086F8ZEM77
Created by admin on Sat Jun 26 03:46:15 UTC 2021 , Edited by admin on Sat Jun 26 03:46:15 UTC 2021
PRIMARY
PUBCHEM
71586916
Created by admin on Sat Jun 26 03:46:15 UTC 2021 , Edited by admin on Sat Jun 26 03:46:15 UTC 2021
PRIMARY
RXCUI
539765
Created by admin on Sat Jun 26 03:46:15 UTC 2021 , Edited by admin on Sat Jun 26 03:46:15 UTC 2021
PRIMARY RxNorm
CAS
7487-74-3
Created by admin on Sat Jun 26 03:46:15 UTC 2021 , Edited by admin on Sat Jun 26 03:46:15 UTC 2021
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY