Naratriptan

drug
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Also known as SID174006312Naratriptan HCl

Summary

Naratriptan (CHEMBL1278) is an approved small-molecule serotonergic agonist (ATC N02CC02) targeting HTR1A, HTR1B, and HTR1D; indicated across 2 conditions including migraine disorder.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: N02CC02
  • Targets: 5 (HTR1A, HTR1B, HTR1D…)
  • Indications: 2 conditions
  • Clinical trials: 9
  • Chemistry: 335.5 Da · C17H25N3O2S

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL1278
NameNaratriptan
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID4440
ChEBICHEBI:7478
ATCN02CC02
Molecular formulaC17H25N3O2S
Molecular weight335.5
InChIKeyAMKVXSZCKVJAGH-UHFFFAOYSA-N

SMILES: CNS(=O)(=O)CCC1=CC2=C(C=C1)NC=C2C3CCN(CC3)C

IUPAC name: N-methyl-2-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]ethanesulfonamide

Pharmacological roles (ChEBI): serotonergic agonist, vasoconstrictor agent.

Also known as: Naratriptan, naratriptan, SID174006312, NARATRIPTAN, Naratriptan HCl

Parent form; salt/anhydrous children: CHEMBL1200601

Patent coverage: 3,067 distinct patent families (12,474 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 12,445 (100%) 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
HTR1A5-HT1A receptorFull agonist7.60%P08908
HTR1B5-HT1B receptorPartial agonist8.10.2%P28222
HTR1D5-HT1D receptorFull agonist90%P28221
HTR1E5-ht1e receptorFull agonist7.70%P28566
HTR1F5-HT1F receptorFull agonist8.20.1%P30939

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: 5-hydroxytryptamine receptor 1B, 5-hydroxytryptamine receptor 1D, 5-hydroxytryptamine receptor 1A.

Bioactivity

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

TargetpChemblTypeValueUnitActivity ID
HTR1B8.82Ki1.5nMCHEMBL_ACT_25553868
HTR1D8.82Ki1.5nMCHEMBL_ACT_25553873
HTR1D8.8EC501.6nMCHEMBL_ACT_771450
HTR1D8.64Ki2.3nMCHEMBL_ACT_771447
HTR1B8.48Ki3.3nMCHEMBL_ACT_771449
HTR1A7.35Ki45nMCHEMBL_ACT_771448

Target pathways

Aggregated over 5 target gene(s): HTR1A, HTR1B, HTR1D, HTR1E, HTR1F.

Top Reactome pathways

8 total, by targets touching each:

PathwayTargetsGenes
Signal Transduction5HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
Signaling by GPCR5HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
Class A/1 (Rhodopsin-like receptors)5HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
Amine ligand-binding receptors5HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
Serotonin receptors5HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
GPCR ligand binding5HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
GPCR downstream signalling4HTR1B, HTR1D, HTR1E, HTR1F
G alpha (i) signalling events4HTR1B, HTR1D, HTR1E, HTR1F

Dominant GO biological processes

GO termTargets
G protein-coupled receptor signaling pathway5
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger5
adenylate cyclase-inhibiting serotonin receptor signaling pathway5
chemical synaptic transmission5
signal transduction5
adenylate cyclase-activating G protein-coupled receptor signaling pathway4
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway4
regulation of behavior3
vasoconstriction2
behavioral fear response1
serotonin receptor signaling pathway1
gamma-aminobutyric acid signaling pathway1
positive regulation of cell population proliferation1
regulation of serotonin secretion1
regulation of vasoconstriction1

Indications & clinical

Indications

2 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
migraine disorder4MONDO:0005277MONDO:0005277

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

Clinical trials

Total trials: 9.

Phase distribution

PhaseTrials
Not specified4
PHASE42
PHASE32
PHASE1/PHASE21

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00282165PHASE4TERMINATEDEfficacy of a Triptan in the Treatment of Hostility and Aggression Among Convicts With a Psychiatric Treatment Order
NCT00487578PHASE4TERMINATEDNaratriptan for the Treatment of Post Traumatic Headache Associated With Cognitive Dysfunction
NCT01390324PHASE3WITHDRAWNEfficacy and Safety of a Fixed-dose Combination of Naratriptan and Naproxen in Acute Treatment of Migraine
NCT01726920PHASE3WITHDRAWNEfficacy and Safety of a Fixed-dose Combination of Naratriptan and Naproxen in Acute Treatment of Migraine.
NCT03066544PHASE1/PHASE2UNKNOWNStatus Migrainosus - Differentiating Between Responders and Non-responders
NCT01059604Not specifiedCOMPLETEDSumatriptan and Naratriptan Pregnancy Registry
NCT01161654Not specifiedCOMPLETEDBioequivalency Study of Naratriptan Hydrochloride 2.5 mg Under Fed Conditions
NCT01332383Not specifiedCOMPLETEDSpecial Drug Use Investigation for AMERGE® Tablet (Long-term)
NCT01376193Not specifiedCOMPLETEDDrug Use Investigation for AMERGE (Naratriptan Hydrochloride) Tablet

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

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.

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

MoleculeSourceStatusShared targets
DIHYDROERGOTAMINEChEMBL + PubChemPhase 4 (approved)HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
ERGOTAMINEChEMBL + PubChemPhase 4 (approved)HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
IMIPRAMINEChEMBL + PubChemPhase 4 (approved)HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
RISPERIDONEChEMBL + PubChemPhase 4 (approved)HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
RIZATRIPTANChEMBL + PubChemPhase 4 (approved)HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
SUMATRIPTANChEMBL + PubChemPhase 4 (approved)HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
ZOLMITRIPTANChEMBL + PubChemPhase 4 (approved)HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
SEROTONINChEMBL + PubChemPhase 3 (approved)HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
YOHIMBINEChEMBL + PubChemPhase 3 (approved)HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
MEBUFOTENINChEMBLPhase 2HTR1A, HTR1B, HTR1D, HTR1E, HTR1F
CLOZAPINEChEMBL + PubChemPhase 4 (approved)HTR1A, HTR1B, HTR1E, HTR1F
ELETRIPTANChEMBL + PubChemPhase 4 (approved)HTR1A, HTR1B, HTR1E, HTR1F
OLANZAPINEChEMBL + PubChemPhase 4 (approved)HTR1A, HTR1B, HTR1E, HTR1F
BREXPIPRAZOLEChEMBLPhase 4 (approved)HTR1A, HTR1B, HTR1D, HTR1E
FROVATRIPTANChEMBLPhase 4 (approved)HTR1A, HTR1B, HTR1D, HTR1E
PSILOCINChEMBLPhase 2HTR1A, HTR1B, HTR1D, HTR1E
CYPROHEPTADINEChEMBL + PubChemPhase 4 (approved)HTR1A, HTR1E, HTR1F
LASMIDITANChEMBL + PubChemPhase 4 (approved)HTR1D, HTR1E, HTR1F
METHYLERGONOVINEChEMBL + PubChemPhase 4 (approved)HTR1A, HTR1E, HTR1F
PRAMIPEXOLEChEMBL + PubChemPhase 4 (approved)HTR1A, HTR1B, HTR1E
QUETIAPINEChEMBL + PubChemPhase 4 (approved)HTR1A, HTR1E, HTR1F
SORAFENIBChEMBL + PubChemPhase 4 (approved)HTR1A, HTR1E, HTR1F
ARIPIPRAZOLEChEMBLPhase 4 (approved)HTR1A, HTR1B, HTR1D
AZELASTINEChEMBLPhase 4 (approved)HTR1B, HTR1D, HTR1E
CARIPRAZINEChEMBLPhase 4 (approved)HTR1A, HTR1B, HTR1D
KETANSERINChEMBLPhase 4 (approved)HTR1A, HTR1B, HTR1D
NEFAZODONEChEMBLPhase 4 (approved)HTR1A, HTR1B, HTR1D
OXYMETAZOLINEChEMBLPhase 4 (approved)HTR1A, HTR1B, HTR1D
SALMETEROLChEMBLPhase 4 (approved)HTR1A, HTR1B, HTR1D
SILODOSINChEMBLPhase 4 (approved)HTR1A, HTR1B, HTR1D
VILAZODONEChEMBLPhase 4 (approved)HTR1A, HTR1B, HTR1D
XYLOMETAZOLINEChEMBLPhase 4 (approved)HTR1A, HTR1B, HTR1D
ACETRYPTINEChEMBLPhase 2HTR1A, HTR1B, HTR1D
GSK163090ChEMBLPhase 2HTR1A, HTR1B, HTR1D
LYSERGIDEChEMBLPhase 2HTR1A, HTR1D, HTR1E
RITANSERINChEMBLPhase 2HTR1A, HTR1B, HTR1E
ASENAPINEChEMBL + PubChemPhase 4 (approved)HTR1A, HTR1E
CANNABIDIOLChEMBL + PubChemPhase 4 (approved)HTR1A, HTR1E
PALIPERIDONEChEMBL + PubChemPhase 4 (approved)HTR1B, HTR1D
ZIPRASIDONEChEMBL + PubChemPhase 4 (approved)HTR1A, HTR1E
CINACALCETChEMBLPhase 4 (approved)HTR1A, HTR1D
LOPERAMIDEChEMBLPhase 4 (approved)HTR1A, HTR1D
MIANSERINChEMBLPhase 4 (approved)HTR1A, HTR1D
PINDOLOLChEMBLPhase 4 (approved)HTR1A, HTR1B
PRAZOSINChEMBLPhase 4 (approved)HTR1A, HTR1D
SERTINDOLEChEMBLPhase 4 (approved)HTR1A, HTR1B
TEGASERODChEMBLPhase 4 (approved)HTR1A, HTR1D
LATREPIRDINEChEMBLPhase 3HTR1D, HTR1E
ALNIDITANChEMBLPhase 2HTR1A, HTR1D
MAZAPERTINEChEMBLPhase 2HTR1A, HTR1B
NIGULDIPINEChEMBLPhase 2HTR1A, HTR1B
PENFLURIDOLChEMBLPhase 2HTR1A, HTR1D
SPIRAMIDEChEMBLPhase 2HTR1A, HTR1D
ACEMETACINChEMBLPhase 4 (approved)HTR1A
ACETOPHENAZINEChEMBLPhase 4 (approved)HTR1A
ACETYLCHOLINEChEMBLPhase 4 (approved)HTR1A
ALMOTRIPTANChEMBLPhase 4 (approved)HTR1A
AMILORIDEChEMBLPhase 4 (approved)HTR1A
AMITRIPTYLINEChEMBLPhase 4 (approved)HTR1A
AMLODIPINEChEMBLPhase 4 (approved)HTR1A