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Details

Stereochemistry ABSOLUTE
Molecular Formula C18H25NO.HI
Molecular Weight 399.3096
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DEXTROMETHORPHAN HYDRIODIDE

SMILES

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

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 271.3972
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

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
Visual hallucinations after combining fluoxetine and dextromethorphan.
1992 Oct
Dextromethorphan- and pseudoephedrine-induced agitated psychosis and ataxia: case report.
1999 Mar-Apr
Mimicking gene defects to treat drug dependence.
2000
The antitussive activity of delta-opioid receptor stimulation in guinea pigs.
2000 Feb
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
Consultation with the specialist: the central serotonin syndrome: paradigm for psychotherapeutic misadventure.
2002 Dec
Expression, purification, biochemical characterization, and comparative function of human cytochrome P450 2D6.1, 2D6.2, 2D6.10, and 2D6.17 allelic isoforms.
2002 Dec
Biotechnology in the Medicon Valley.
2002 May
Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain.
2003 Dec 9
Total and corrected antioxidant capacity in hemodialyzed patients.
2003 Jul 1
Combined phenotypic assessment of cytochrome p450 1A2, 2C9, 2C19, 2D6, and 3A, N-acetyltransferase-2, and xanthine oxidase activities with the "Cooperstown 5+1 cocktail".
2003 Nov
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
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
Evaluation of fresh and cryopreserved hepatocytes as in vitro drug metabolism tools for the prediction of metabolic clearance.
2004 Nov
Characterization of microsomal cytochrome P450-dependent monooxygenases in the rat olfactory mucosa.
2005 Aug
MK-801 and dextromethorphan block microglial activation and protect against methamphetamine-induced neurotoxicity.
2005 Jul 19
Co-administration of dextromethorphan with methamphetamine attenuates methamphetamine-induced rewarding and behavioral sensitization.
2006 Sep
Bench-to-bedside review: mechanisms and management of hyperthermia due to toxicity.
2007
Treatment of the common cold.
2007 Feb 15
Free energies of binding of R- and S-propranolol to wild-type and F483A mutant cytochrome P450 2D6 from molecular dynamics simulations.
2007 Jul
Dextromethorphan: a review of N-methyl-d-aspartate receptor antagonist in the management of pain.
2007 Spring
Effects of common antitussive drugs on the hERG potassium channel current.
2008 Dec
Effects of repeated cycles of sterilisation on the mechanical characteristics of titanium miniplates for osteosynthesis.
2008 Sep
Characterization of retrieved orthodontic miniscrew implants.
2009 Jan
Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: the NNIPPS study.
2009 Jan
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 Fri Dec 15 15:11:01 GMT 2023
Edited
by admin
on Fri Dec 15 15:11:01 GMT 2023
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 Fri Dec 15 15:11:01 GMT 2023 , Edited by admin on Fri Dec 15 15:11:01 GMT 2023
PRIMARY
FDA UNII
086F8ZEM77
Created by admin on Fri Dec 15 15:11:01 GMT 2023 , Edited by admin on Fri Dec 15 15:11:01 GMT 2023
PRIMARY
PUBCHEM
71586916
Created by admin on Fri Dec 15 15:11:01 GMT 2023 , Edited by admin on Fri Dec 15 15:11:01 GMT 2023
PRIMARY
RXCUI
539765
Created by admin on Fri Dec 15 15:11:01 GMT 2023 , Edited by admin on Fri Dec 15 15:11:01 GMT 2023
PRIMARY RxNorm
CAS
7487-74-3
Created by admin on Fri Dec 15 15:11:01 GMT 2023 , Edited by admin on Fri Dec 15 15:11:01 GMT 2023
PRIMARY
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