NARATRIPTAN

First approved in 1998

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H25N3O2S
Molecular Weight	335.464
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=AMKVXSZCKVJAGH-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Molecular Formula	C17H25N3O2S
Molecular Weight	335.464
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.drugbank.ca/drugs/DB00952 | https://www.ncbi.nlm.nih.gov/pubmed/16389295
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/1998/20763lbl.pdf

Naratriptan (trade names include Amerge and Naramig) is a triptan drug marketed by GlaxoSmithKline and is used for the treatment of migraine headaches.Naratriptan is a selective agonist of serotonin (5-hydroxytryptamine; 5-HT) type 1B and 1D receptors. It is structurally and pharmacologically related to other selective 5-HT1B/1D receptor agonist. Naratriptan has only a weak affinity for 5-HT1A, 5-HT5A, and 5-HT7 receptors and no significant affinity or pharmacological activity at 5-HT2, 5-HT3 or 5-HT4 receptor subtypes or at alpha1-, alpha2-, or beta-adrenergic, dopamine1,; dopamine2; muscarinic, or benzodiazepine receptors. This action in humans correlates with the relief of migraine headache. In addition to causing vasoconstriction, experimental data from animal studies show that Naratriptan also activates 5-HT1 receptors on peripheral terminals of the trigeminal nerve innervating cranial blood vessels, which may also contribute to the antimigrainous effect of Naratriptan in humans.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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotonin 1d (5-HT1d) receptor 53 Target ID: CHEMBL1983 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16389295 \| http://www.accessdata.fda.gov/drugsatfda_docs/label/1998/20763lbl.pdf	Agonist 2752		1.6 nM [EC50]
Serotonin 1b (5-HT1b) receptor 45 Target ID: CHEMBL1898 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16389295 \| http://www.accessdata.fda.gov/drugsatfda_docs/label/1998/20763lbl.pdf	Agonist 2752		23.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Migraine 107 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/1998/20763lbl.pdf https://www.ncbi.nlm.nih.gov/pubmed/16389295	Primary		Approved 8583	AMERGE Approved Use Naratriptan is indicated for the acute treatment of migraine attacks with or without aura in adults. Launch Date 1998

C_max

Value	Dose	Co-administered	Analyte	Population
7.97 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11210397/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:		NARATRIPTAN serum	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: FASTED
92 ng/mL EXPERIMENT https://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502011000100003&lang=en	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:		NARATRIPTAN plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
74.6 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11210397/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:		NARATRIPTAN serum	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: FASTED
107.97 ng × h/mL EXPERIMENT https://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502011000100003&lang=en	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:		NARATRIPTAN plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11210397/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:		NARATRIPTAN serum	Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
10 mg 1 times / day single, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: single Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20763_Amerge_Medr_P1.pdf	unhealthy, 39 Health Status: unhealthy Age Group: 39 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20763_Amerge_Medr_P1.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20763_Amerge_Medr_P1.pdf
2.5 mg 3 times / day multiple, oral Recommended Dose: 2.5 mg, 3 times / day Route: oral Route: multiple Dose: 2.5 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20763_Amerge_Medr_P1.pdf	unhealthy, 40.4 Health Status: unhealthy Age Group: 40.4 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20763_Amerge_Medr_P1.pdf	Disc. AE: Abdominal pain... AEs leading to discontinuation/dose reduction: Abdominal pain Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20763_Amerge_Medr_P1.pdf

AEs

AE	Significance	Dose	Population
Abdominal pain	Disc. AE	2.5 mg 3 times / day multiple, oral Recommended Dose: 2.5 mg, 3 times / day Route: oral Route: multiple Dose: 2.5 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20763_Amerge_Medr_P1.pdf	unhealthy, 40.4 Health Status: unhealthy Age Group: 40.4 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20763_Amerge_Medr_P1.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252	substrate 1193 inhibitor 2438	substrate 1388 inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2B6 926 CYP2C19 2057 CYP2E1 1060 OATP1A2 43	CYP2C19 1119 P-gp 2052 CYP1A2 1197 CYP2A6 626 CYP2B6 776 CYP2C8 810 CYP2E1 729 OCT1 393

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	no [IC50 >100 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	no [IC50 >100 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	no [IC50 >100 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	no [IC50 >100 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	no [IC50 >100 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	weak [IC50 40 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	weak [IC50 84 uM]
OATP1A2 43	inhibitor 4027 Sources: https://papyrus.bib.umontreal.ca/xmlui/bitstream/handle/1866/19272/Lu_Jennifer_2016_these.pdf?sequence=2&isAllowed=y#page=112 Page: 112.0	yes [IC50 5.5 uM]

Drug as victim

Target	Modality	Activity
CYP2A6 626	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	no
CYP2B6 776	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	no
CYP2E1 729	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	no
CYP2C8 810	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	poor
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	yes
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	yes
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	yes
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	yes
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	yes
OCT1 393	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/26659468/ Page: -	yes
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:7478	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:7478
ChemicalBook	CB1874790	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1874790
eMolecules	36516764	https://www.emolecules.com/cgi-bin/more?vid=36516764
MolPort	MolPort-005-932-823	https://www.molport.com/shop/molecule-link/MolPort-005-932-823
ZINC	ZINC000000004076	http://zinc15.docking.org/substances/ZINC000000004076

PubMed

Title	Date	PubMed
The use of multiattribute decision models in evaluating triptan treatment options in migraine.	2005-09	15761676
Correlation between lipophilicity and triptan outcomes.	2005-01	15663606
Colonic ischemia associated with naratriptan use.	2004-10	15365406
[Meta-analysis of triptan treatment in migraine].	2004-09	15552863
Activation of 5-HT(1B/1D) receptor in the periaqueductal gray inhibits nociception.	2004-09	15349864
The sumatriptan/naratriptan aggregated patient (SNAP) database: aggregation, validation and application.	2004-07	15196301
Involvement of 5-HT1B receptors in triptan-induced contractile responses in guinea-pig isolated iliac artery.	2004-07	15185063
Efficacy of quality criteria to identify potentially harmful information: a cross-sectional survey of complementary and alternative medicine web sites.	2004-06-29	15249270
Rizatriptan versus rizatriptan plus rofecoxib versus rizatriptan plus tolfenamic acid in the acute treatment of migraine.	2004-06-28	15222892
Patterns of use of triptans and reasons for switching them in a tertiary care migraine population.	2004-06-24	15209687
Migraine headache.	2004-06	15652076
Transformed migraine and medication overuse in a tertiary headache centre--clinical characteristics and treatment outcomes.	2004-06	15154858
Triptans and CNS side-effects: pharmacokinetic and metabolic mechanisms.	2004-06	15154851
Cost considerations of acute migraine treatment.	2004-03	15012668
The 5-hydroxytryptamine1B/1D/1F receptor agonists eletriptan and naratriptan inhibit trigeminovascular input to the nucleus tractus solitarius in the cat.	2004-02-13	14725972
[Recent progress in therapy for migraine headache].	2004-02-10	15007953
Naratriptan for the treatment of acute migraine: meta-analysis of randomised controlled trials.	2004-02	14998068
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.	2004-02	14728705
Triptans and gastric accommodation: pharmacological and therapeutic aspects.	2004-01	14971822
[Treatment of migraine].	2004	15484860
Migraine headache.	2003-12	15555160
Out-patient detoxification in chronic migraine: comparison of strategies.	2003-12	14984232
Comparative efficacy of eletriptan and zolmitriptan in the acute treatment of migraine.	2003-12	14984226
Meta-analysis of oral triptan therapy for migraine: number needed to treat and relative cost to achieve relief within 2 hours.	2003-11-14	14613361
Comparative efficacy of eletriptan vs. naratriptan in the acute treatment of migraine.	2003-11	14616928
Managing intractable migraine with naratriptan.	2003-10	14511276
Investigation of the effects of naratriptan, rizatriptan, and sumatriptan on jugular venous oxygen saturation in anesthetized pigs: implications for their mechanism of acute antimigraine action.	2003-10	12954804
Migraine: diagnosis and management.	2003-09-27	14511196
Effects of naratriptan versus naproxen on daily functioning in the acute treatment of migraine: a randomized, double-blind, double-dummy, crossover study.	2003-09	12940805
Eletriptan metabolism by human hepatic CYP450 enzymes and transport by human P-glycoprotein.	2003-07	12814962
S+ -flurbiprofen but not 5-HT1 agonists suppress basal and stimulated CGRP and PGE2 release from isolated rat dura mater.	2003-06	12791437
[Highly selective beginning. Associated symptoms and side effects in retrospect].	2003-05-26	14579499
[Improved pharmacokinetics. Fast tryptan with sustained response].	2003-05-26	14579498
[A descriptive analysis of naratriptan use among migraineurs in ambulatory medicine].	2003-05	12773900
Naratriptan in the preventive treatment of refractory chronic migraine: a review of 27 cases.	2003-05	12752754
Demographic and migraine characteristics of adolescents with migraine: Glaxo Wellcome clinical trials' database.	2003-05	12752749
Migraine: pathophysiology, pharmacology, treatment and future trends.	2003-03	15320857
Safety profile of the triptans.	2003-03	12904112
[Early, but not unnecessarily frequent administration. What is proper timing for triptan drugs?].	2003-01-16	12638444
Coprescription of triptans with potentially interacting medications: a cohort study involving 240,268 patients.	2003-01	12864757
Evidence for serotonin (5-HT)1B, 5-HT1D and 5-HT1F receptor inhibitory effects on trigeminal neurons with craniovascular input.	2003	14614913
Newer formulations of the triptans: advances in migraine management.	2003	14524731
Pharmacological approaches to migraine.	2003	12830928
Naratriptan in the preventive treatment of cluster headache.	2002-12	12485208
Gateways to clinical trials.	2002-11	12616707
[Ischemic colitis associated with naratriptan administration].	2002-11	12483146
An introduction to migraine: from ancient treatment to functional pharmacology and antimigraine therapy.	2002	12434581
Comparative aspects of triptans in treating migraine.	2001	12739316
Naratriptan.	2001	12463278
Sumatriptan: pharmacological basis and clinical results.	2001	12463276

Patents

Sample Use Guides

In Vivo Use Guide

Initial dose: 1 mg or 2.5 mg orally, once -Provided there has been some response to first dose, a second dose may be administered at least 4 hours later if migraine returns or symptoms recur. Maximum dose: 5 mg in a 24-hour period

Route of Administration: Oral

In Vitro Use Guide

Naratriptan (10, 100 uM) inhibited vasocontractile responses in rabbit common carotid artery to sumatriptan with a pKb value of 5.9+0.2 or eletriptan with a pKb value of 5.7+0.7 in CCA

Substance Class	Chemical Created by `admin` on `Wed Apr 02 09:42:26 GMT 2025` Edited by `admin` on `Wed Apr 02 09:42:26 GMT 2025`
Record UNII	QX3KXL1ZA2
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NARATRIPTAN

Official Name

English

NARAMIG

Preferred Name

English

1H-INDOLE-5-ETHANESULFONAMIDE, N-METHYL-3-(1-METHYL-4-PIPERIDINYL)-

Systematic Name

English

NARATRIPTAN [VANDF]

Common Name

English

Naratriptan [WHO-DD]

Common Name

English

NARATRIPTAN [MI]

Common Name

English

naratriptan [INN]

Common Name

English

NARATRIPTAN [ORANGE BOOK]

Common Name

English

N-METHYL-2-(3-(1-METHYLPIPERIDEN-4-YL)INDOLE-5-YL)ETHANESULFONAMIDE

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175763