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
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
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/27139517Curator'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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27139517
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.
CNS Activity
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24678061
Curator's Comment: # in a Swiss and US patent application from Hoffmann-La Roche in 1946 and 1947, respectively
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL287 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15723099 |
205.0 nM [Ki] | ||
Target ID: CHEMBL4787 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2897648 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | MUCINEX DM Approved UseHelps 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 Date1.08319677E12 |
|||
Primary | NUEDEXTA Approved UseNUEDEXTA 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 Date1.28580479E12 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15342614/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15342614/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15342614/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15342614/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15342614/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15342614/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15342614/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15342614/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15342614/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
32 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15342614/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15342614/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15342614/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15342614/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15342614/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15342614/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15342614/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15342614/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15342614/ |
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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01361217 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
13.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15342614/ |
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
Dose | Population | Adverse 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 |
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 |
unknown, 27 years n = 1 Health Status: unknown Age Group: 27 years Sex: M Population Size: 1 Sources: |
Other AEs: Ischemic colitis... |
270 mg single, oral Overdose |
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) Sources: Ataxia (1 patient) Nystagmus (1 patient) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Ischemic colitis | 1 patient | 900 mg single, oral Overdose |
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 |
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 |
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 |
unknown, 3 years n = 1 Health Status: unknown Age Group: 3 years Sex: M Population Size: 1 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no | |||
Page: 14.0 |
no |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/11602530/ Page: 2.0 |
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/021879Orig1s000OtherR.pdf#page=63 Page: 63.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Visual hallucinations after combining fluoxetine and dextromethorphan. | 1992 Oct |
|
Dextromethorphan and its metabolite dextrorphan block alpha3beta4 neuronal nicotinic receptors. | 2000 Jun |
|
The role of glutamatergic transmission in the pathogenesis of levodopa-induced dyskinesias. Potential therapeutic approaches. | 2001 |
|
Prediction models in the design of neural network based ECG classifiers: a neural network and genetic programming approach. | 2002 |
|
A sensitive LC-MS/MS assay for the determination of dextromethorphan and metabolites in human urine--application for drug interaction studies assessing potential CYP3A and CYP2D6 inhibition. | 2002 Aug 22 |
|
Expression, purification, biochemical characterization, and comparative function of human cytochrome P450 2D6.1, 2D6.2, 2D6.10, and 2D6.17 allelic isoforms. | 2002 Dec |
|
Dextromethorphan is effective in the treatment of subacute methotrexate neurotoxicity. | 2002 Jul-Aug |
|
Substrate specificity for rat cytochrome P450 (CYP) isoforms: screening with cDNA-expressed systems of the rat. | 2002 Mar 1 |
|
Dextromethorphan and memantine in painful diabetic neuropathy and postherpetic neuralgia: efficacy and dose-response trials. | 2002 May |
|
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 |
|
Evaluation of the One-Step ELISA kit for the detection of buprenorphine in urine, blood, and hair specimens. | 2004 Jul 16 |
|
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 |
|
Bladder emptying over a period of 10-45 years after a traumatic spinal cord injury. | 2004 Nov |
|
Evaluation of fresh and cryopreserved hepatocytes as in vitro drug metabolism tools for the prediction of metabolic clearance. | 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 |
|
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 |
|
Effect of dextrometorphan and dextrorphan on nicotine and neuronal nicotinic receptors: in vitro and in vivo selectivity. | 2005 Feb |
|
Dextromethorphan-induced delirium and possible methadone interaction. | 2005 Mar |
|
Side effects of dextromethorphan abuse, a case series. | 2005 Sep |
|
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 |
|
Treatment of the common cold. | 2007 Feb 15 |
|
Oral administration of dextromethorphan does not produce neuronal vacuolation in the rat brain. | 2007 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 |
|
[Bone anchored hearing aids (BAHA)]. | 2009 Mar |
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 Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24912029
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.
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Classification Tree | Code System | Code | ||
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NDF-RT |
N0000181821
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CFR |
21 CFR 341.14
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CFR |
21 CFR 341.74
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WHO-VATC |
QN07XX59
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WHO-VATC |
QR05DA09
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WHO-ATC |
R05DA09
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NDF-RT |
N0000182149
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WHO-ATC |
N07XX59
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NCI_THESAURUS |
C2199
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Code System | Code | Type | Description | ||
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1180503
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C62022
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751452
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M4227
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PRIMARY | Merck Index | ||
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166
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N0000181819
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PRIMARY | Uncompetitive NMDA Receptor Antagonists [MoA] | ||
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4470
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DTXSID3022908
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3056
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125-71-3
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SUB07051MIG
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204-752-2
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CHEMBL52440
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N0000182147
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PRIMARY | Sigma-1 Receptor Agonists [MoA] | ||
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842
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DB00514
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6953
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7355X3ROTS
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Dextromethorphan
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7355X3ROTS
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3289
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ALTERNATIVE | RxNorm | ||
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DEXTROMETHORPHAN
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100000092321
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D003915
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5360696
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236146
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE ACTIVE (PARENT)
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)