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Dextromethorphan

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Also known as DextromethorphaneDextrometorfanoDimetane-dxNSC-751452dextrometorphanSID11111057SID50100218DextromorphanDEXTROMETHORPHAN HYDROBROMIDE

Summary

Dextromethorphan (CHEMBL52440) is an approved small-molecule NMDA receptor antagonist (ATC N07XX59) targeting SIGMAR1, GRIN2C, and TAS2R1; indicated across 40 conditions including opiate dependence and proteinuria.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: N07XX59 (+1 more)
  • Targets: 3 (SIGMAR1, GRIN2C, TAS2R1)
  • Indications: 40 conditions
  • Clinical trials: 108
  • Chemistry: 271.4 Da · C18H25NO

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL52440
NameDextromethorphan
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID5360696
ChEBICHEBI:4470
ATCN07XX59, R05DA09
Molecular formulaC18H25NO
Molecular weight271.4
InChIKeyMKXZASYAUGDDCJ-NJAFHUGGSA-N

SMILES: CN1CC[C@@]23CCCC[C@@H]2[C@@H]1CC4=C3C=C(C=C4)OC

IUPAC name: (1S,9S,10S)-4-methoxy-17-methyl-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-triene

ChEBI definition: A 6-methoxy-11-methyl-1,3,4,9,10,10a-hexahydro-2H-10,4a-(epiminoethano)phenanthrene in which the sterocenters at positions 4a, 10 and 10a have S-configuration. It is a prodrug of dextrorphan and used as an antitussive drug for suppressing cough.

Pharmacological roles (ChEBI): NMDA receptor antagonist, neurotoxin, antitussive, prodrug, oneirogen.

Other ChEBI roles (chemical / environmental): xenobiotic, environmental contaminant.

Also known as: Dextromethorphan, Dextromethorphane, Dextrometorfano, Dimetane-dx, NSC-751452, dextrometorphan, dextromethorphan, SID11111057, SID50100218, DEXTROMETHORPHAN, Dextromorphan, DEXTROMETHORPHAN HYDROBROMIDE

Parent form; salt/anhydrous children: CHEMBL1201461, CHEMBL1256818, CHEMBL3989940, CHEMBL3989946

Patent coverage: 9,789 distinct patent families (33,223 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 32,854 (99%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
SIGMAR1sigma non-opioid intracellular receptor 1Agonist6.282.6%Q99720
GRIN2CGluN2C6.330.2%Q14957
TAS2R1TAS2R1Agonist0%Q9NYW7

Broader ChEMBL bioactivity targets: 31 (assay-derived). Sample: 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Neuronal acetylcholine receptor; alpha3/beta4, Glutamate NMDA receptor; GRIN1/GRIN2B, Glutamate NMDA receptor; GRIN1/GRIN2A, Glutamate NMDA receptor, Alpha-2C adrenergic receptor, Thyrotropin receptor, Glutamate [NMDA] receptor, Sodium channel alpha subunits; brain (Types I, II, III).

Bioactivity

ChEMBL activities: 39 potent at pChembl ≥ 5 of 55 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
SLC6A48.84Ki1.44nMCHEMBL_ACT_7698203
SLC6A48.57IC502.71nMCHEMBL_ACT_7698202
TSHR8.2Potency6.3nMCHEMBL_ACT_3937164
TSHR8.2Potency6.3nMCHEMBL_ACT_4739322
Q604928Ki10nMCHEMBL_ACT_22992922
Q604927.82IC5015.2nMCHEMBL_ACT_2089400
CYP2D67.39IC5040.8nMCHEMBL_ACT_24822374
CYP2D67.39IC5041nMCHEMBL_ACT_25593409
CYP2D67.37IC5043nMCHEMBL_ACT_24740410
CYP2D67.28IC5052nMCHEMBL_ACT_25502134
Q604927.2Ki63nMCHEMBL_ACT_22992812
SLC6A46.89AC50130nMCHEMBL_ACT_25149960
Q604926.63IC50232nMCHEMBL_ACT_2089402
CYP2D66.62IC50242nMCHEMBL_ACT_26109722
SIGMAR16.46Ki348nMCHEMBL_ACT_306979
GRIN15.98IC501040nMCHEMBL_ACT_29194982
P047745.89IC501300nMCHEMBL_ACT_1108113
P354395.88IC501320nMCHEMBL_ACT_15718257
GRIN2D5.78Ki1680nMCHEMBL_ACT_857929
CYP2D65.75IC501800nMCHEMBL_ACT_713624
P354395.65Ki2246nMCHEMBL_ACT_755960
CYP2D65.6Potency2512nMCHEMBL_ACT_5006468
CYP2D65.6AC502512nMCHEMBL_ACT_6054497
OPRM15.57AC502700nMCHEMBL_ACT_25157192
P354395.53AC502944nMCHEMBL_ACT_25120265
OPRK15.53AC502968nMCHEMBL_ACT_25129081
MRGPRX25.49EC503236nMCHEMBL_ACT_26241767
CYP2D65.47IC503400nMCHEMBL_ACT_1701456
ADRA1A5.45AC503579nMCHEMBL_ACT_25137702
P084825.4Potency3981nMCHEMBL_ACT_4811330

Target pathways

Aggregated over 3 target gene(s): SIGMAR1, GRIN2C, TAS2R1.

Top Reactome pathways

20 total, by targets touching each:

PathwayTargetsGenes
Signal Transduction1TAS2R1
Disease1SIGMAR1
Signaling by GPCR1TAS2R1
GPCR downstream signalling1TAS2R1
G alpha (i) signalling events1TAS2R1
Class C/3 (Metabotropic glutamate/pheromone receptors)1TAS2R1
Unblocking of NMDA receptors, glutamate binding and activation1GRIN2C
GPCR ligand binding1TAS2R1
Infectious disease1SIGMAR1
Neurexins and neuroligins1GRIN2C
Synaptic adhesion-like molecules1GRIN2C
Assembly and cell surface presentation of NMDA receptors1GRIN2C
Negative regulation of NMDA receptor-mediated neuronal transmission1GRIN2C
Long-term potentiation1GRIN2C
Potential therapeutics for SARS1SIGMAR1
SARS-CoV Infections1SIGMAR1
Sensory Perception1TAS2R1
Sensory perception of taste1TAS2R1
Sensory perception of sweet, bitter, and umami (glutamate) taste1TAS2R1
Viral Infection Pathways1SIGMAR1

Dominant GO biological processes

GO termTargets
lipid transport1
nervous system development1
regulation of neuron apoptotic process1
protein homotrimerization1
response to alcohol1
regulation of postsynapse assembly1
G protein-coupled opioid receptor signaling pathway1
glutamate receptor signaling pathway1
brain development1
response to wounding1
directional locomotion1
ionotropic glutamate receptor signaling pathway1
synaptic transmission, glutamatergic1
negative regulation of protein catabolic process1
regulation of synaptic plasticity1

Indications & clinical

Indications

40 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
opiate dependence3MONDO:0005530EFO:0005611
proteinuria3MONDO:0003634HP:0000093
relapsing-remitting multiple sclerosis3MONDO:0005314EFO:0003929
amyotrophic lateral sclerosis3MONDO:0004976MONDO:0004976
multiple sclerosis3MONDO:0005301MONDO:0005301
Rett syndrome3MONDO:0010726MONDO:0010726
bipolar disorder3MONDO:0004985MONDO:0004985
peripheral neuropathy2MONDO:0005244EFO:0003100
neuralgia2MONDO:0021667EFO:0005762
irritable bowel syndrome2MONDO:0005052EFO:0000555
autism2MONDO:0005260EFO:0003758
diabetic neuropathy2MONDO:0006626EFO:1000783
fibromyalgia2MONDO:0005546EFO:0005687
major depressive disorder2MONDO:0002009MONDO:0002009
drug dependence2MONDO:0005303EFO:0003890
type 2 diabetes mellitus2MONDO:0005148MONDO:0005148
Parkinson disease2MONDO:0005180MONDO:0005180
neurodegenerative disease2MONDO:0005559EFO:0005772
Crohn disease1MONDO:0005011EFO:0000384
neoplasm1MONDO:0005070EFO:0000616
psoriasis1MONDO:0005083EFO:0000676
HIV infectious disease1MONDO:0005109EFO:0000764
cytomegalovirus infection1MONDO:0005132EFO:0001062
metastatic melanoma1MONDO:0005191EFO:0002617
voice disorders1MONDO:0043862EFO:0009692
ulcerative colitis1MONDO:0005101EFO:0000729
malaria1MONDO:0005136EFO:0001068
common cold1MONDO:0005709EFO:0007214
Alzheimer disease1MONDO:0004975MONDO:0004975
inborn mitochondrial metabolism disorder1MONDO:0004069MONDO:0044970
melanoma1MONDO:0005105EFO:0000756
trypanosomiasis1MONDO:0000940DOID:10113

8 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 108.

Phase distribution

PhaseTrials
PHASE142
PHASE221
Not specified16
PHASE413
PHASE39
PHASE1/PHASE23
PHASE2/PHASE32
EARLY_PHASE12

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00513864PHASE4WITHDRAWNAssessment of Opioid Analgesia in Sickle Cell
NCT00605605PHASE4COMPLETEDVascular Endothelial Protection Effects of Dextromethorphan
NCT01257542PHASE4TERMINATEDAcute Cough Study In Children
NCT01766050PHASE4COMPLETEDStudy to Evaluate Effect of Belatacept on Pharmacokinetics of Inje Cocktail in Healthy Volunteers
NCT02651116PHASE4TERMINATEDDextromethorphan Pediatric Acute Cough Study
NCT02727491PHASE4COMPLETEDDoes Pre and Postoperative Dextromethorphan Reduce Post-tonsillectomy Pain in Children?
NCT02760615PHASE4WITHDRAWNPhase 4, Vedolizumab-4002 Post-marketing, Disease-Drug-Drug Interaction Study
NCT02987920PHASE4TERMINATEDDextromethorphan Use in Multimodal Analgesia Regimens for Total Knee Arthroplasty
NCT03076021PHASE4COMPLETEDEffects of Isotretinoin on CYP2D6 Activity
NCT03738917PHASE4COMPLETEDEffectiveness of Antitussives, Anticholinergics and Honey Versus Usual Care in Adults With Acute Bronchitis.
NCT05043805PHASE4UNKNOWNDextromethorphan Added on for Children With Chronic Irritability
NCT05181527PHASE4COMPLETEDRepurposing of Dextromethorphan as an Adjunct Therapy in Patients With Major Depressive Disorder
NCT05944510PHASE4COMPLETEDDextromethorphan as an Augmentation Agent in Treatment-resistant Schizophrenia
NCT06958692PHASE3RECRUITINGA Trial of Dextromethorphan and Bupropion Sustained-Release Tablets in Patients With Major Depressive Disorder
NCT00003687PHASE3COMPLETEDTreatment for Chronic Pain in Patients With Advanced Cancer
NCT00069550PHASE3UNKNOWNIndependent Studies of Dextromethorphan and of Donepezil Hydrochloride for Rett Syndrome
NCT01091324PHASE3UNKNOWNDextromethorphan and Silymarin in Chronic Kidney Disease (CKD) Patients
NCT01188265PHASE3COMPLETEDAdd-on Dextromethorphan in Bipolar Disorders
NCT01189006PHASE2/PHASE3COMPLETEDAdd-On Therapy to Risperidonein Schizophrenia
NCT01189097PHASE3UNKNOWNCombined Therapy of Methadone and Dextromethrophan
NCT01462318PHASE3COMPLETEDAn Open-Label Immunogenicity and Pharmacokinetics Study of Daclizumab High Yield Process Prefilled Syringe in Relapsing Remitting Multiple Sclerosis
NCT03039842PHASE3UNKNOWNCombination of Dextromethorphan and Memantine in Treating Bipolar Disorder
NCT03480009PHASE3COMPLETEDDextromethorphan as a Novel Non-opioid Adjunctive Agent for Pain Control in Medication Abortion
NCT04687566PHASE2/PHASE3UNKNOWNDextromethorphan, Memantine Monotherapy, or Combined Use of Dextromethorphan and Memantine in Amphetamine Addiction
NCT04899687PHASE2RECRUITINGStudy of Dextromethorphan in OCD and Related Disorders
NCT07583589PHASE2NOT_YET_RECRUITINGNintedanib With or Without Dextromethorphan in Patients With Idiopathic Pulmonary Fibrosis (IPF)
NCT00000352PHASE2COMPLETEDEffects of Dextromethorphan on Opioid Tolerance in Methadone Patients - 1
NCT00001344PHASE2COMPLETEDDextromethorphan Versus Placebo for Neuropathic Pain
NCT00001365PHASE2COMPLETEDDextromethorphan for the Treatment of Parkinson’s Disease and Similar Conditions of the Nervous System
NCT00001725PHASE2COMPLETEDStudies of Dextromethorphan and Topiramate to Treat Oral and Facial Pain
NCT00108446PHASE2COMPLETEDCharacterization of Pain Processing Mechanisms in Irritable Bowel Syndrome
NCT00359281PHASE2COMPLETEDPharmacokinetic Drug Interactions of AEGR-733 on Lipid-lowering Agents
NCT00593957PHASE2TERMINATEDTrial of Dextromethorphan in Rett Syndrome
NCT01435798PHASE2COMPLETEDClinical Neuropharmacology of Pain in Spinal Cord Injury- Dextromethorphan Dose Response Clinical Trial
NCT01441102PHASE1/PHASE2COMPLETEDDextromethorphan for Diabetic Macular Edema
NCT01441986PHASE2COMPLETEDDextromethorphan, Amantadine and Glucose Homeostasis in Diabetes Subjects
NCT01520363PHASE2COMPLETEDPlacebo Controlled Trial of Dextromethorphan in Rett Syndrome
NCT01882829PHASE2COMPLETEDNuedexta in Treatment-Resistant Major Depression
NCT01936025PHASE2COMPLETEDA Study to Investigate the Glucose Lowering Effects of Dextromethorphan Alone or in Combination With Sitagliptin in Subjects With Type 2 Diabetes Mellitus (T2DM) After an Oral Glucose Tolerance Test
NCT02142712PHASE2COMPLETEDHistamine Glutamate Antagonism in Stroke

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 7 clinical and 106 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

169 molecules share ≥1 primary target. Top 60 by shared-target count:

MoleculeSourceStatusShared targets
AMANTADINEChEMBL + PubChemPhase 4 (approved)GRIN2C, SIGMAR1
CHLORPROMAZINEChEMBL + PubChemPhase 4 (approved)GRIN2C, SIGMAR1
IFENPRODILChEMBLPhase 2GRIN2C, SIGMAR1
PHENCYCLIDINEChEMBLPhase 2GRIN2C, SIGMAR1
KETAMINEChEMBL + PubChemPhase 4 (approved)GRIN2C
LEVORPHANOLChEMBL + PubChemPhase 4 (approved)GRIN2C
MEMANTINEChEMBL + PubChemPhase 4 (approved)GRIN2C
METHAMPHETAMINEChEMBL + PubChemPhase 4 (approved)SIGMAR1
ORPHENADRINEChEMBL + PubChemPhase 4 (approved)GRIN2C
AMIODARONEChEMBLPhase 4 (approved)SIGMAR1
AMITRIPTYLINEChEMBLPhase 4 (approved)SIGMAR1
ASTEMIZOLEChEMBLPhase 4 (approved)SIGMAR1
AZELASTINEChEMBLPhase 4 (approved)SIGMAR1
BENZTROPINEChEMBLPhase 4 (approved)SIGMAR1
BETAXOLOLChEMBLPhase 4 (approved)SIGMAR1
BREXPIPRAZOLEChEMBLPhase 4 (approved)SIGMAR1
BROMHEXINEChEMBLPhase 4 (approved)SIGMAR1
BUFLOMEDILChEMBLPhase 4 (approved)SIGMAR1
BUSPIRONEChEMBLPhase 4 (approved)SIGMAR1
BUTENAFINEChEMBLPhase 4 (approved)SIGMAR1
CARBETAPENTANEChEMBLPhase 4 (approved)SIGMAR1
CHLOROQUINEChEMBLPhase 4 (approved)SIGMAR1
CINACALCETChEMBLPhase 4 (approved)SIGMAR1
CINNARIZINEChEMBLPhase 4 (approved)SIGMAR1
CISAPRIDEChEMBLPhase 4 (approved)SIGMAR1
CITALOPRAMChEMBLPhase 4 (approved)SIGMAR1
CLEMASTINEChEMBLPhase 4 (approved)SIGMAR1
CLOMIPRAMINEChEMBLPhase 4 (approved)SIGMAR1
CLOZAPINEChEMBLPhase 4 (approved)SIGMAR1
COCAINEChEMBLPhase 4 (approved)SIGMAR1
CYCLOSERINEChEMBLPhase 4 (approved)GRIN2C
DEXCHLORPHENIRAMINEChEMBLPhase 4 (approved)SIGMAR1
DEXFENFLURAMINEChEMBLPhase 4 (approved)SIGMAR1
DICYCLOMINEChEMBLPhase 4 (approved)SIGMAR1
DIHYDROERGOTAMINEChEMBLPhase 4 (approved)SIGMAR1
DIMENHYDRINATEChEMBLPhase 4 (approved)SIGMAR1
DIPHENIDOLChEMBLPhase 4 (approved)SIGMAR1
DOBUTAMINEChEMBLPhase 4 (approved)SIGMAR1
DONEPEZILChEMBLPhase 4 (approved)SIGMAR1
DOXEPINChEMBLPhase 4 (approved)SIGMAR1
ECONAZOLEChEMBLPhase 4 (approved)SIGMAR1
FENTANYLChEMBLPhase 4 (approved)SIGMAR1
FLUOXETINEChEMBLPhase 4 (approved)SIGMAR1
FLUPHENAZINEChEMBLPhase 4 (approved)SIGMAR1
FLUVOXAMINEChEMBLPhase 4 (approved)SIGMAR1
HALOPERIDOLChEMBLPhase 4 (approved)SIGMAR1
HYDROXYCHLOROQUINEChEMBLPhase 4 (approved)SIGMAR1
ILOPERIDONEChEMBLPhase 4 (approved)SIGMAR1
ISOPROTERENOLChEMBLPhase 4 (approved)TAS2R1
KETANSERINChEMBLPhase 4 (approved)SIGMAR1
LABETALOLChEMBLPhase 4 (approved)SIGMAR1
LASMIDITANChEMBLPhase 4 (approved)SIGMAR1
LEVAMFETAMINEChEMBLPhase 4 (approved)SIGMAR1
LEVOBUNOLOLChEMBLPhase 4 (approved)SIGMAR1
LOPERAMIDEChEMBLPhase 4 (approved)SIGMAR1
MAZINDOLChEMBLPhase 4 (approved)SIGMAR1
MEPAZINEChEMBLPhase 4 (approved)SIGMAR1
METHYSERGIDEChEMBLPhase 4 (approved)SIGMAR1
MIFEPRISTONEChEMBLPhase 4 (approved)SIGMAR1
NAFTIFINEChEMBLPhase 4 (approved)SIGMAR1

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
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Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot