Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C18H25NO.BrH |
Molecular Weight | 352.309 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 3 / 3 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Br.[H][C@]12CCCC[C@]13CCN(C)[C@H]2CC4=CC=C(OC)C=C34
InChI
InChIKey=MISZALMBODQYFT-URVXVIKDSA-N
InChI=1S/C18H25NO.BrH/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
Molecular Formula | BrH |
Molecular Weight | 80.912 |
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 |
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 Date2004 |
|||
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 Date2010 |
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 |
---|---|---|
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 |
|
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 |
|
Effect of dextromethorphan, diphenhydramine, and placebo on nocturnal cough and sleep quality for coughing children and their parents. | 2004 Jul |
|
Comparison of various urine collection intervals for caffeine and dextromethorphan phenotyping in children. | 2004 Jul |
|
Evaluation of the One-Step ELISA kit for the detection of buprenorphine in urine, blood, and hair specimens. | 2004 Jul 16 |
|
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 |
|
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 |
|
Characterization of microsomal cytochrome P450-dependent monooxygenases in the rat olfactory mucosa. | 2005 Aug |
|
Dextromethorphan psychosis, dependence and physical withdrawal. | 2005 Dec |
|
MK-801 and dextromethorphan block microglial activation and protect against methamphetamine-induced neurotoxicity. | 2005 Jul 19 |
|
Cytochrome P450 2D6 (CYP2D6) inhibitory constituents of Catharanthus roseus. | 2005 Jun |
|
Dextromethorphan-induced delirium and possible methadone interaction. | 2005 Mar |
|
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 |
|
Cough mixture abuse as a novel cause of folate deficiency: a prospective, community-based, controlled study. | 2007 Apr |
|
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 |
|
Comparative metabolic capabilities and inhibitory profiles of CYP2D6.1, CYP2D6.10, and CYP2D6.17. | 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 |
|
Free energies of binding of R- and S-propranolol to wild-type and F483A mutant cytochrome P450 2D6 from molecular dynamics simulations. | 2007 Jul |
|
Challenges for Australia's Bio/Nanopharma Policies: trade deals, public goods and reference pricing in sustainable industrial renewal. | 2007 Jun 1 |
|
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 |
|
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 |
|
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 |
|
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 |
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.
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 17:19:08 GMT 2023
by
admin
on
Fri Dec 15 17:19:08 GMT 2023
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Record UNII |
Z0CG3115FG
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Record Status |
Validated (UNII)
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Record Version |
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-
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5464025
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125-69-9
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Z0CG3115FG
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DTXSID60872346
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756723
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m4227
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PRIMARY | Merck Index |
Related Record | Type | Details | ||
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PARENT -> SALT/SOLVATE | |||
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SOLVATE->ANHYDROUS |
Related Record | Type | Details | ||
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ACTIVE MOIETY |