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

Details

Stereochemistry ABSOLUTE
Molecular Formula C76H52O46.C18H25NO
Molecular Weight 1972.5957
Optical Activity UNSPECIFIED
Defined Stereocenters 8 / 8
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DEXTROMETHORPHAN TANNATE

SMILES

[H][C@]12CCCC[C@]13CCN(C)[C@H]2CC4=CC=C(OC)C=C34.OC5=CC(=CC(O)=C5O)C(=O)OC6=CC(=CC(O)=C6O)C(=O)OC[C@H]7O[C@@H](OC(=O)C8=CC(O)=C(O)C(OC(=O)C9=CC(O)=C(O)C(O)=C9)=C8)[C@H](OC(=O)C%10=CC(O)=C(O)C(OC(=O)C%11=CC(O)=C(O)C(O)=C%11)=C%10)[C@@H](OC(=O)C%12=CC(O)=C(O)C(OC(=O)C%13=CC(O)=C(O)C(O)=C%13)=C%12)[C@@H]7OC(=O)C%14=CC(O)=C(O)C(OC(=O)C%15=CC(O)=C(O)C(O)=C%15)=C%14

InChI

InChIKey=HFUQPPONNTXWAO-VVRPOUSDSA-N
InChI=1S/C76H52O46.C18H25NO/c77-32-1-22(2-33(78)53(32)92)67(103)113-47-16-27(11-42(87)58(47)97)66(102)112-21-52-63(119-72(108)28-12-43(88)59(98)48(17-28)114-68(104)23-3-34(79)54(93)35(80)4-23)64(120-73(109)29-13-44(89)60(99)49(18-29)115-69(105)24-5-36(81)55(94)37(82)6-24)65(121-74(110)30-14-45(90)61(100)50(19-30)116-70(106)25-7-38(83)56(95)39(84)8-25)76(118-52)122-75(111)31-15-46(91)62(101)51(20-31)117-71(107)26-9-40(85)57(96)41(86)10-26;1-19-10-9-18-8-4-3-5-15(18)17(19)11-13-6-7-14(20-2)12-16(13)18/h1-20,52,63-65,76-101H,21H2;6-7,12,15,17H,3-5,8-11H2,1-2H3/t52-,63-,64+,65-,76+;15-,17+,18+/m11/s1

HIDE SMILES / InChI

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

Molecular Formula C76H52O46
Molecular Weight 1701.1985
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
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
Molecular and ligand-binding characterization of the sigma-receptor in the Jurkat human T lymphocyte cell line.
1999 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
Dextromethorphan- and pseudoephedrine-induced agitated psychosis and ataxia: case report.
1999 Mar-Apr
[Acute cholestatic hepatitis induced by dextromethorphan].
1999 Oct
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
Prediction models in the design of neural network based ECG classifiers: a neural network and genetic programming approach.
2002
Evaluation of cytochrome P450 probe substrates commonly used by the pharmaceutical industry to study in vitro drug interactions.
2002 Dec
Dextromethorphan and memantine in painful diabetic neuropathy and postherpetic neuralgia: efficacy and dose-response trials.
2002 May
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
Validated assays for human cytochrome P450 activities.
2004 Jun
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
Dimemorfan prevents seizures induced by the L-type calcium channel activator BAY k-8644 in mice.
2004 May 5
Evaluation of fresh and cryopreserved hepatocytes as in vitro drug metabolism tools for the prediction of metabolic clearance.
2004 Nov
[Dextromethorphan enhances analgesic activity of propacetamol--experimental study].
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
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
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
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
Oral administration of dextromethorphan does not produce neuronal vacuolation in the rat brain.
2007 Jul
Effect of sodium ozagrel on the activity of rat CYP2D6.
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
Sex differences in NMDA antagonist enhancement of morphine antihyperalgesia in a capsaicin model of persistent pain: comparisons to two models of acute pain.
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
Life-threatening dextromethorphan intoxication associated with interaction with amitriptyline in a poor CYP2D6 metabolizer: a single case re-exposure study.
2008 Jul
Effects of repeated cycles of sterilisation on the mechanical characteristics of titanium miniplates for osteosynthesis.
2008 Sep
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.
Substance Class Chemical
Created
by admin
on Fri Dec 15 20:19:40 GMT 2023
Edited
by admin
on Fri Dec 15 20:19:40 GMT 2023
Record UNII
554R584P9K
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DEXTROMETHORPHAN TANNATE
WHO-DD  
Common Name English
DEXTROMETHORPHAN TANNATE [WHO-DD]
Common Name English
3-METHOXY-17-METHYL-9.ALPHA.,13.ALPHA.,14.ALPHA.-MORPHINAN TANNATE
Common Name English
Code System Code Type Description
PUBCHEM
16214284
Created by admin on Fri Dec 15 20:19:40 GMT 2023 , Edited by admin on Fri Dec 15 20:19:40 GMT 2023
PRIMARY
CAS
1406-78-6
Created by admin on Fri Dec 15 20:19:40 GMT 2023 , Edited by admin on Fri Dec 15 20:19:40 GMT 2023
PRIMARY
FDA UNII
554R584P9K
Created by admin on Fri Dec 15 20:19:40 GMT 2023 , Edited by admin on Fri Dec 15 20:19:40 GMT 2023
PRIMARY
SMS_ID
100000177090
Created by admin on Fri Dec 15 20:19:40 GMT 2023 , Edited by admin on Fri Dec 15 20:19:40 GMT 2023
PRIMARY
RXCUI
259262
Created by admin on Fri Dec 15 20:19:40 GMT 2023 , Edited by admin on Fri Dec 15 20:19:40 GMT 2023
PRIMARY RxNorm
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