Dextromethorphan

Sigma-1 Agonist — NERVOUS SYSTEM

Key facts

Dextromethorphan is an ofp drug in the Sigma-1 Agonist class catalogued in DrugCentral. It was first approved by the FDA in 1957. Its mechanism of action is classified as Sigma-1 Receptor Agonists and Uncompetitive NMDA Receptor Antagonists. DrugCentral lists 12 molecular targets, including SLC6A4, SIGMAR1 and SIGMAR1. Recorded indications include Allergic rhinitis, Common cold, Cough and Fever.

• Approval status: ofp (first approved 1957 by the FDA).
• Drug class: Sigma-1 Agonist; Uncompetitive N-methyl-D-aspartate Receptor Antagonist.
• Mechanism of action: Sigma-1 Receptor Agonists; Uncompetitive NMDA Receptor Antagonists.
• Molecular targets: SLC6A4, SIGMAR1, SIGMAR1 and GRIN2C (12 listed in DrugCentral).
• Indications: Allergic rhinitis, Common cold, Cough, Fever and Headache disorder and others.
• ATC code: N06AX62 (Other antidepressants).
• Molecular formula: C18H25NO; molecular weight 271.40 g/mol.

Indications & contraindications

Drug–disease relationships curated by DrugCentral (OMOP / SNOMED concepts).

Indications (15)

• Allergic rhinitis
• Common cold
• Cough
• Fever
• Headache disorder
• Influenza-like symptoms
• Major depressive disorder
• Mouth Irritation
• Nasal congestion
• Nasal discharge
• Pseudobulbar affect
• Rhinitis
• Sneezing
• Sore throat symptom
• Vasomotor rhinitis

Contraindications (85)

• Achalasia of esophagus
• Acidosis
• Acute abdominal pain
• Acute hepatitis
• Acute nephropathy
• Acute pancreatitis
• Acute tuberculosis
• Adrenal cortical hypofunction
• Alcohol intoxication
• Alcohol withdrawal delirium
• Alcoholism
• Anemia due to enzyme deficiency
• Angle-closure glaucoma
• Anuria
• Arterial thrombosis
• Arteriosclerotic vascular disease
• Asthenia
• Atony of colon
• Autonomic dysreflexia
• Azotemia
• Benign intracranial hypertension
• Benign prostatic hyperplasia
• Bladder outflow obstruction
• Bleeding
• Bone marrow depression
• Bradycardia
• Brain damage
• Breastfeeding (mother)
• Bronchitis
• Central nervous system depression
• + 55 more

Mechanism & targets

• Mechanism of action (MoA): Sigma-1 Receptor Agonists; Uncompetitive NMDA Receptor Antagonists
• Established pharmacologic class: Sigma-1 Agonist; Uncompetitive N-methyl-D-aspartate Receptor Antagonist

Molecular targets (12)

Target	Gene	Action	Activity
Sodium-dependent serotonin transporter	SLC6A4	unknown	Ki 8.84
Sigma non-opioid intracellular receptor 1	SIGMAR1	unknown	IC50 7.82
Sigma non-opioid intracellular receptor 1	SIGMAR1	agonist	D2 6.46
Glutamate receptor ionotropic, NMDA 2C	GRIN2C	blocker	IC50 6.33
Sodium channel alpha subunits; brain (Types I, II, III)	Scn1a|Scn2a|Scn3a	unknown	IC50 5.89
Glutamate receptor ionotropic, NMDA 3A	GRIN3A	antagonist	IC50 5.70
Glutamate NMDA receptor	Grin1|Grin2a|Grin2b|Grin2c|Grin2d|Grin3b|Grin3a	unknown	Ki 5.65
Sigma non-opioid intracellular receptor 1	Sigmar1	unknown	Ki 5.29
Solute carrier family 22 member 1	SLC22A1	unknown	IC50 4.98
Sodium-dependent noradrenaline transporter	SLC6A2	unknown	IC50 4.78
Taste receptor type 2 member 46	TAS2R46	unknown	EC50 4.51
Cytochrome P450 2D6	CYP2D6	unknown	Ks 4.48

Regulatory approvals (1)

Date	Agency	Marketed as	Applicant	Orphan
1957-12-03	FDA	—	ANI PHARMS

ATC classification

ATC code	Therapeutic hierarchy
N06AX62	NERVOUS SYSTEM › PSYCHOANALEPTICS › ANTIDEPRESSANTS › Other antidepressants
N07XX59	NERVOUS SYSTEM › OTHER NERVOUS SYSTEM DRUGS › OTHER NERVOUS SYSTEM DRUGS › Other nervous system drugs
R05DA09	RESPIRATORY SYSTEM › COUGH AND COLD PREPARATIONS › COUGH SUPPRESSANTS, EXCL. COMBINATIONS WITH EXPECTORANTS › Opium alkaloids and derivatives

Pharmacogenomics

Drug-label and guideline annotations from PharmGKB and CPIC.

• Swissmedic label: CYP2D6 · Actionable PGx

Reported adverse-event signals

Strongest FDA FAERS disproportionality signals (log-likelihood ratio). A signal is a statistical association in spontaneous reports, not proof that the drug causes the event.

MedDRA term	LLR
Toxicity to various agents	8096.8
Completed suicide	4901.4
Exposure to toxic agent	2983.0
Intentional overdose	2875.6
Overdose	2773.6
Acute hepatic failure	2534.7
Infusion related reaction	1581.3
Blood pressure fluctuation	1286.2
Hepatic cytolysis	1089.3
Suicide attempt	1046.6
Intentional product misuse	957.1
Drug ineffective	832.1

Chemical structure

Full physicochemical, ADMET and 3D-structure analysis of Dextromethorphan is on its molecule page.

• Molecular formula: C₁₈H₂₅NO
• Molecular weight: 271.40 g/mol
• CAS number: 125-71-3
• InChIKey: MKXZASYAUGDDCJ-NJAFHUGGSA-N
• PubChem CID: 5360696

COC1=CC2=C(C[C@H]3[C@H]4CCCC[C@@]24CCN3C)C=C1

Frequently asked questions

Answers are generated from the structured data on this page, not written by hand.

What is Dextromethorphan used for?

DrugCentral lists the following indications for Dextromethorphan: Allergic rhinitis, Common cold, Cough, Fever, Headache disorder, Influenza-like symptoms, Major depressive disorder and Mouth Irritation and others.

How does Dextromethorphan work?

Dextromethorphan is classified as Sigma-1 Receptor Agonists and Uncompetitive NMDA Receptor Antagonists; its molecular targets in DrugCentral include SLC6A4, SIGMAR1, SIGMAR1 (agonist) and GRIN2C (blocker).

When was Dextromethorphan first approved?

Dextromethorphan was first approved by the FDA in 1957.

What drug class does Dextromethorphan belong to?

Dextromethorphan is in the Sigma-1 Agonist class.

What is the chemical formula of Dextromethorphan?

Dextromethorphan has the molecular formula C18H25NO and a molecular weight of 271.40 g/mol.

Sources

• DrugCentral drug card 842 — structure, indications, targets, approvals, pharmacologic classes (CC BY-SA 4.0)
• ChEMBL CHEMBL1201461 — compound record and bioactivity
• PubChem CID 5360696 — chemical identifiers
• DrugBank DB00514 — drug record
• FDA UNII 7355X3ROTS — substance identity
• DailyMed: FDA labels for Dextromethorphan — current prescribing information (label search)
• UniProt P31645 (SLC6A4) — target protein
• UniProt Q99720 (SIGMAR1) — target protein
• UniProt Q14957 (GRIN2C) — target protein
• UniProt Q8TCU5 (GRIN3A) — target protein
• UniProt O15245 (SLC22A1) — target protein
• UniProt P23975 (SLC6A2) — target protein
• FDA Adverse Event Reporting System (openFDA FAERS) — adverse-event signals, as aggregated by DrugCentral
• PharmGKB / CPIC — pharmacogenomic label annotations

How this page is built: methodology · editorial policy & corrections.