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Record Information
Version2.0
Creation Date2009-07-21 20:28:01 UTC
Update Date2014-12-24 20:25:53 UTC
Accession NumberT3D2939
Identification
Common NameNaratriptan
ClassSmall Molecule
DescriptionNaratriptan is only found in individuals that have used or taken this drug. It is a triptan drug used for the treatment of migraine headaches. It is a selective 5-hydroxytryptamine1 receptor subtype agonist.Three distinct pharmacological actions have been implicated in the antimigraine effect of the triptans: (1) stimulation of presynaptic 5-HT1D receptors, which serves to inhibit both dural vasodilation and inflammation; (2) direct inhibition of trigeminal nuclei cell excitability via 5-HT1B/1D receptor agonism in the brainstem and (3) vasoconstriction of meningeal, dural, cerebral or pial vessels as a result of vascular 5-HT1B receptor agonism.
Compound Type
  • Amide
  • Amine
  • Drug
  • Metabolite
  • Organic Compound
  • Selective Serotonin Agonist
  • Serotonin Agonist
  • Serotonin Antagonist
  • Serotonin Receptor Agonist
  • Synthetic Compound
  • Vasoconstrictor Agent
Chemical Structure
Thumb
Synonyms
Synonym
Amerge
N-Methyl-2-(3-(1-methylpiperiden-4-yl)indole-5-yl)ethanesulfonamide
N-Methyl-2-[3-(1-methyl-4-piperidyl)-1H-indol-5-yl]-ethanesulfonamide
Naramig
Naratriptanum
Chemical FormulaC17H25N3O2S
Average Molecular Mass335.464 g/mol
Monoisotopic Mass335.167 g/mol
CAS Registry Number121679-13-8
IUPAC NameN-methyl-2-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]ethane-1-sulfonamide
Traditional Namenaratriptan
SMILESCNS(=O)(=O)CCC1=CC2=C(NC=C2C2CCN(C)CC2)C=C1
InChI IdentifierInChI=1S/C17H25N3O2S/c1-18-23(21,22)10-7-13-3-4-17-15(11-13)16(12-19-17)14-5-8-20(2)9-6-14/h3-4,11-12,14,18-19H,5-10H2,1-2H3
InChI KeyInChIKey=AMKVXSZCKVJAGH-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as 3-alkylindoles. 3-alkylindoles are compounds containing an indole moiety that carries an alkyl chain at the 3-position.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIndoles and derivatives
Sub ClassIndoles
Direct Parent3-alkylindoles
Alternative Parents
Substituents
  • 3-alkylindole
  • Aralkylamine
  • Piperidine
  • Substituted pyrrole
  • Organic sulfonic acid amide
  • Benzenoid
  • Organosulfonic acid amide
  • Pyrrole
  • Organic sulfonic acid or derivatives
  • Heteroaromatic compound
  • Organosulfonic acid or derivatives
  • Aminosulfonyl compound
  • Sulfonyl
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organosulfur compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point246°C (HCl salt)
Boiling PointNot Available
Solubility35 mg/mL
LogP1.6
Predicted Properties
PropertyValueSource
Water Solubility0.11 g/LALOGPS
logP2.16ALOGPS
logP1.44ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)11.55ChemAxon
pKa (Strongest Basic)9.18ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area65.2 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity94.26 m³·mol⁻¹ChemAxon
Polarizability38 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0563-6592000000-ddbcdc8fb1564ab67954JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0079-0019000000-6a6e24b9a465404217cbJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-052f-5196000000-d65d77c315f42655bc94JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00dj-9181000000-5426adb0583eefe0387dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-2009000000-94e23cf10a35640e1665JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-056r-9047000000-e204b450ea7d67367377JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-03fu-9010000000-4168e596b68161b1f564JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0009000000-eb77fa3eb994fd4f881eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-0091000000-3e0656c2932e26031087JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001j-8974000000-f06f269baa785ea29ed4JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-0009000000-0fe6fb135327a243d85bJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001l-1096000000-9e82cb949d18ff9c097dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0200-2091000000-28483e9f079277138f81JSpectraViewer
Toxicity Profile
Route of ExposureWell absorbed (74% oral biovaility), absorption is rapid with peak plasma concentrations after 2-5 hours. The rate of absorption is slower during a migraine attack.
Mechanism of ToxicityThree distinct pharmacological actions have been implicated in the antimigraine effect of the triptans: (1) stimulation of presynaptic 5-HT1D receptors, which serves to inhibit both dural vasodilation and inflammation; (2) direct inhibition of trigeminal nuclei cell excitability via 5-HT1B/1D receptor agonism in the brainstem and (3) vasoconstriction of meningeal, dural, cerebral or pial vessels as a result of vascular 5-HT1B receptor agonism.
MetabolismPrimarily hepatic. In vitro, naratriptan is metabolized by a wide range of cytochrome P450 isoenzymes into a number of inactive metabolites. Half Life: 5-8 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the acute treatment of migraine attacks with or without aura in adults.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overdose include light-headedness, loss of coordination, tension in the neck, and tiredness.
TreatmentThere is no specific antidote to naratriptan. Standard supportive treatment should be applied as required. If the patient presents with chest pain or other symptoms consistent with angina pectoris, ECG monitoring should be performed for evidence of ischemia. (5)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00952
HMDB IDHMDB15087
PubChem Compound ID4440
ChEMBL IDCHEMBL1278
ChemSpider ID4287
KEGG IDC07792
UniProt IDNot Available
OMIM ID
ChEBI ID7478
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNaratriptan
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNaratriptan
References
Synthesis Reference

Dharmaraj Ramachandra Rao, Rajendra Narayanrao Kankan, Sandip Vasant Chikhalikar, Maruti Ghagare, “Process for the synthesis of naratriptan.” U.S. Patent US20120220778, issued August 30, 2012.

MSDSLink
General References
  1. Massiou H: Naratriptan. Curr Med Res Opin. 2001;17 Suppl 1:s51-3. [12463278 ]
  2. Lambert GA: Preclinical neuropharmacology of naratriptan. CNS Drug Rev. 2005 Autumn;11(3):289-316. [16389295 ]
  3. Villalon CM, Centurion D, Valdivia LF, de Vries P, Saxena PR: Migraine: pathophysiology, pharmacology, treatment and future trends. Curr Vasc Pharmacol. 2003 Mar;1(1):71-84. [15320857 ]
  4. Drugs.com [Link]
  5. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances, such as lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Regulates the release of 5-hydroxytryptamine, dopamine and acetylcholine in the brain, and thereby affects neural activity, nociceptive processing, pain perception, mood and behavior. Besides, plays a role in vasoconstriction of cerebral arteries.
Gene Name:
HTR1B
Uniprot ID:
P28222
Molecular Weight:
43567.535 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.0033 uMNot AvailableBindingDB 50073682
Inhibitory0.0051 uMNot AvailableBindingDB 50073682
Inhibitory0.0094 uMNot AvailableBindingDB 50073682
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Pauwels PJ, Palmier C, Dupuis DS, Colpaert FC: Interaction of 5-HT1B/D ligands with recombinant h 5-HT1A receptors: intrinsic activity and modulation by G-protein activation state. Naunyn Schmiedebergs Arch Pharmacol. 1998 May;357(5):490-9. [9650800 ]
  3. Akin D, Onaran HO, Gurdal H: Agonist-directed trafficking explaining the difference between response pattern of naratriptan and sumatriptan in rabbit common carotid artery. Br J Pharmacol. 2002 May;136(2):171-6. [12010764 ]
  4. Hoskin KL, Lambert GA, Donaldson C, Zagami AS: The 5-hydroxytryptamine1B/1D/1F receptor agonists eletriptan and naratriptan inhibit trigeminovascular input to the nucleus tractus solitarius in the cat. Brain Res. 2004 Feb 13;998(1):91-9. [14725972 ]
  5. Boers PM, Donaldson C, Zagami AS, Lambert GA: Naratriptan has a selective inhibitory effect on trigeminovascular neurones at central 5-HT1A and 5-HT(1B/1D) receptors in the cat: implications for migraine therapy. Cephalalgia. 2004 Feb;24(2):99-109. [14728705 ]
  6. Xu YC, Schaus JM, Walker C, Krushinski J, Adham N, Zgombick JM, Liang SX, Kohlman DT, Audia JE: N-Methyl-5-tert-butyltryptamine: A novel, highly potent 5-HT1D receptor agonist. J Med Chem. 1999 Feb 11;42(3):526-31. [9986723 ]
  7. Domenech T, Beleta J, Palacios JM: Characterization of human serotonin 1D and 1B receptors using [3H]-GR-125743, a novel radiolabelled serotonin 5HT1D/1B receptor antagonist. Naunyn Schmiedebergs Arch Pharmacol. 1997 Sep;356(3):328-34. [9303569 ]
  8. Connor HE, Feniuk W, Beattie DT, North PC, Oxford AW, Saynor DA, Humphrey PP: Naratriptan: biological profile in animal models relevant to migraine. Cephalalgia. 1997 May;17(3):145-52. [9170336 ]
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Regulates the release of 5-hydroxytryptamine in the brain, and thereby affects neural activity. May also play a role in regulating the release of other neurotransmitters. May play a role in vasoconstriction.
Gene Name:
HTR1D
Uniprot ID:
P28221
Molecular Weight:
41906.38 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.0015 uMNot AvailableBindingDB 50073682
Inhibitory0.0023 uMNot AvailableBindingDB 50073682
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Hargreaves RJ, Shepheard SL: Pathophysiology of migraine--new insights. Can J Neurol Sci. 1999 Nov;26 Suppl 3:S12-9. [10563228 ]
  3. Donaldson C, Boers PM, Hoskin KL, Zagami AS, Lambert GA: The role of 5-HT1B and 5-HT1D receptors in the selective inhibitory effect of naratriptan on trigeminovascular neurons. Neuropharmacology. 2002 Mar;42(3):374-85. [11897116 ]
  4. Pauwels PJ, Colpaert FC: Selective antagonism of human 5-HT1D and 5-HT1B receptor-mediated responses in stably transfected C6-glial cells by ketanserin and GR 127,935. Eur J Pharmacol. 1996 Apr 4;300(1-2):141-5. [8741180 ]
  5. Domenech T, Beleta J, Palacios JM: Characterization of human serotonin 1D and 1B receptors using [3H]-GR-125743, a novel radiolabelled serotonin 5HT1D/1B receptor antagonist. Naunyn Schmiedebergs Arch Pharmacol. 1997 Sep;356(3):328-34. [9303569 ]
  6. Xu YC, Schaus JM, Walker C, Krushinski J, Adham N, Zgombick JM, Liang SX, Kohlman DT, Audia JE: N-Methyl-5-tert-butyltryptamine: A novel, highly potent 5-HT1D receptor agonist. J Med Chem. 1999 Feb 11;42(3):526-31. [9986723 ]
  7. Connor HE, Feniuk W, Beattie DT, North PC, Oxford AW, Saynor DA, Humphrey PP: Naratriptan: biological profile in animal models relevant to migraine. Cephalalgia. 1997 May;17(3):145-52. [9170336 ]
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.
Gene Name:
HTR1A
Uniprot ID:
P08908
Molecular Weight:
46106.335 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.045 uMNot AvailableBindingDB 50073682
References
  1. Tfelt-Hansen P, De Vries P, Saxena PR: Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy. Drugs. 2000 Dec;60(6):1259-87. [11152011 ]
  2. Xu YC, Schaus JM, Walker C, Krushinski J, Adham N, Zgombick JM, Liang SX, Kohlman DT, Audia JE: N-Methyl-5-tert-butyltryptamine: A novel, highly potent 5-HT1D receptor agonist. J Med Chem. 1999 Feb 11;42(3):526-31. [9986723 ]
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity.
Gene Name:
HTR1F
Uniprot ID:
P30939
Molecular Weight:
41708.505 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]