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 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 |
---|---|---|
The need for rational therapeutics in the use of cough and cold medicine in infants. | 1992 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 |
|
[Acute cholestatic hepatitis induced by dextromethorphan]. | 1999 Oct |
|
Mimicking gene defects to treat drug dependence. | 2000 |
|
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 |
|
Evaluation of cytochrome P450 probe substrates commonly used by the pharmaceutical industry to study in vitro drug interactions. | 2002 Dec |
|
Bridging sectors. Medicon Valley. | 2002 Dec 12 |
|
Biotechnology in the Medicon Valley. | 2002 May |
|
Dextromethorphan and memantine in painful diabetic neuropathy and postherpetic neuralgia: efficacy and dose-response trials. | 2002 May |
|
Non-competitive NMDA receptor antagonists moderate seizure-induced c-fos expression in the rat cerebral cortex. | 2003 Feb 15 |
|
Total and corrected antioxidant capacity in hemodialyzed patients. | 2003 Jul 1 |
|
mRNA and protein expression of dog liver cytochromes P450 in relation to the metabolism of human CYP2C substrates. | 2003 Mar |
|
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 |
|
Effect of dextromethorphan, diphenhydramine, and placebo on nocturnal cough and sleep quality for coughing children and their parents. | 2004 Jul |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
Immunohistological assessment of the synovial tissue in small joints in rheumatoid arthritis: validation of a minimally invasive ultrasound-guided synovial biopsy procedure. | 2007 |
|
Cough mixture abuse as a novel cause of folate deficiency: a prospective, community-based, controlled study. | 2007 Apr |
|
Effects of dextromethorphan on dopamine dependent behaviours in rats. | 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 |
|
Prior exposure to uninfected mosquitoes enhances mortality in naturally-transmitted West Nile virus infection. | 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 |
|
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 |
|
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 |
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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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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DEXTROMETHORPHAN
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100000092321
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D003915
Created by
admin on Fri Dec 15 15:04:42 GMT 2023 , Edited by admin on Fri Dec 15 15:04:42 GMT 2023
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5360696
Created by
admin on Fri Dec 15 15:04:42 GMT 2023 , Edited by admin on Fri Dec 15 15:04:42 GMT 2023
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236146
Created by
admin on Fri Dec 15 15:04:42 GMT 2023 , Edited by admin on Fri Dec 15 15:04:42 GMT 2023
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