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
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
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 |
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 |
---|---|---|
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 |
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 20:19:40 GMT 2023
by
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on
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Record UNII |
554R584P9K
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Record Status |
Validated (UNII)
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Record Version |
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PARENT -> SALT/SOLVATE |
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ACTIVE MOIETY |
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