T3DB: Naratriptan

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (4)XML

Targets (4)

Record Information

Version

2.0

Creation Date

2009-07-21 20:28:01 UTC

Update Date

2014-12-24 20:25:53 UTC

Accession Number

T3D2939

Identification

Common Name

Naratriptan

Class

Small Molecule

Description

Naratriptan 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

MOL SDF PDB SMILES InChI

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 Formula

C₁₇H₂₅N₃O₂S

Average Molecular Mass

335.464 g/mol

Monoisotopic Mass

335.167 g/mol

CAS Registry Number

121679-13-8

IUPAC Name

N-methyl-2-[3-(1-methylpiperidin-4-yl)-1H-indol-5-yl]ethane-1-sulfonamide

Traditional Name

naratriptan

SMILES

CNS(=O)(=O)CCC1=CC2=C(NC=C2C2CCN(C)CC2)C=C1

InChI Identifier

InChI=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 Key

InChIKey=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.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Indoles and derivatives

Sub Class

Indoles

Direct Parent

3-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 Framework

Aromatic heteropolycyclic compounds

External Descriptors

sulfonamide (CHEBI:7478 )
tryptamines (CHEBI:7478 )
heteroarylpiperidine (CHEBI:7478 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Biological Roles

serotonergic agonist

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	246°C (HCl salt)
Boiling Point	Not Available
Solubility	35 mg/mL
LogP	1.6

Predicted Properties

Property	Value	Source
Water Solubility	0.11 g/L	ALOGPS
logP	2.16	ALOGPS
logP	1.44	ChemAxon
logS	-3.5	ALOGPS
pKa (Strongest Acidic)	11.55	ChemAxon
pKa (Strongest Basic)	9.18	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	65.2 Å²	ChemAxon
Rotatable Bond Count	4	ChemAxon
Refractivity	94.26 m³·mol⁻¹	ChemAxon
Polarizability	38 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0563-6592000000-ddbcdc8fb1564ab67954	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0079-0019000000-6a6e24b9a465404217cb	2016-08-02	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-052f-5196000000-d65d77c315f42655bc94	2016-08-02	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-00dj-9181000000-5426adb0583eefe0387d	2016-08-02	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-001i-2009000000-94e23cf10a35640e1665	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-056r-9047000000-e204b450ea7d67367377	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-03fu-9010000000-4168e596b68161b1f564	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-000i-0009000000-eb77fa3eb994fd4f881e	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-03di-0091000000-3e0656c2932e26031087	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-001j-8974000000-f06f269baa785ea29ed4	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-001i-0009000000-0fe6fb135327a243d85b	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-001l-1096000000-9e82cb949d18ff9c097d	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0200-2091000000-28483e9f079277138f81	2021-10-11	View Spectrum

Toxicity Profile

Route of Exposure

Well 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 Toxicity

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.

Metabolism

Primarily 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 Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

For the acute treatment of migraine attacks with or without aura in adults.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Symptoms of overdose include light-headedness, loss of coordination, tension in the neck, and tiredness.

Treatment

There 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

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

7478

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Naratriptan

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Naratriptan

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.

MSDS

Link

General References

Massiou H: Naratriptan. Curr Med Res Opin. 2001;17 Suppl 1:s51-3. [12463278 ]
Lambert GA: Preclinical neuropharmacology of naratriptan. CNS Drug Rev. 2005 Autumn;11(3):289-316. [16389295 ]
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 ]
Drugs.com [Link]
RxList: The Internet Drug Index (2009). [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. 5-hydroxytryptamine receptor 1B

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

Type	Value	Assay Type	Assay Source
Inhibitory	0.0033 uM	Not Available	BindingDB 50073682
Inhibitory	0.0051 uM	Not Available	BindingDB 50073682
Inhibitory	0.0094 uM	Not Available	BindingDB 50073682

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]

Target Details

2. 5-hydroxytryptamine receptor 1D

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

Type	Value	Assay Type	Assay Source
Inhibitory	0.0015 uM	Not Available	BindingDB 50073682
Inhibitory	0.0023 uM	Not Available	BindingDB 50073682

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Hargreaves RJ, Shepheard SL: Pathophysiology of migraine--new insights. Can J Neurol Sci. 1999 Nov;26 Suppl 3:S12-9. [10563228 ]
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 ]
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 ]
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 ]
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 ]
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 ]

Target Details

3. 5-hydroxytryptamine receptor 1A

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

Type	Value	Assay Type	Assay Source
Inhibitory	0.045 uM	Not Available	BindingDB 50073682

References

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 ]
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 ]

Target Details

4. 5-hydroxytryptamine receptor 1F

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

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]

Naratriptan (T3D2939)

Structure for T3D2939: Naratriptan

Targets

Binding/Activity Constants

References

Binding/Activity Constants

References

Binding/Activity Constants

References

References