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

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 52 Target ID: CHEMBL1983 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16389295 \| http://www.accessdata.fda.gov/drugsatfda_docs/label/1998/20763lbl.pdf	Agonist 2678		1.6 nM [EC50]
Serotonin 1b (5-HT1b) receptor 46 Target ID: CHEMBL1898 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16389295 \| http://www.accessdata.fda.gov/drugsatfda_docs/label/1998/20763lbl.pdf	Agonist 2678		23.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Migraine 103 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/1998/20763lbl.pdf https://www.ncbi.nlm.nih.gov/pubmed/16389295	Primary		Approved 8429	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 Page: Study 2004	unhealthy, 39 n = 96 Health Status: unhealthy Condition: migraine Age Group: 39 Sex: M+F Population Size: 96 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20763_Amerge_Medr_P1.pdf Page: Study 2004	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20763_Amerge_Medr_P1.pdf Page: Study 2004
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 Page: Study 3002	unhealthy, 40.4 n = 127 Health Status: unhealthy Condition: migraine Age Group: 40.4 Sex: M+F Population Size: 127 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20763_Amerge_Medr_P1.pdf Page: Study 3002	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 Page: Study 3002

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 Page: Study 3002	unhealthy, 40.4 n = 127 Health Status: unhealthy Condition: migraine Age Group: 40.4 Sex: M+F Population Size: 127 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20763_Amerge_Medr_P1.pdf Page: Study 3002

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	substrate 1037 inhibitor 1767	substrate 1217 inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2B6 810 CYP2C19 1478 CYP2E1 882 OATP1A2 35	CYP2C19 991 P-gp 1537 CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2E1 667 OCT1 327

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	no [IC50 >100 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	no [IC50 >100 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	no [IC50 >100 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	no [IC50 >100 uM]
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	no [IC50 >100 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	weak [IC50 40 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	weak [IC50 84 uM]
OATP1A2 35	inhibitor 3277 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 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	no
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	no
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	no
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	poor
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	yes
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	yes
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	yes
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	yes
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/12814962/ Page: -	yes
OCT1 327	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26659468/ Page: -	yes
P-gp 1537	substrate 3367 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
MolPort	MolPort-005-932-823	https://www.molport.com/shop/molecule-link/MolPort-005-932-823
ZINC	ZINC000000004076	http://zinc15.docking.org/substances/ZINC000000004076
eMolecules	36516764	https://www.emolecules.com/cgi-bin/more?vid=36516764

PubMed

Title	Date	PubMed
Characterisation of the 5-HT receptor binding profile of eletriptan and kinetics of [3H]eletriptan binding at human 5-HT1B and 5-HT1D receptors.	1999 Mar 5	10193663
Comparison of naratriptan and sumatriptan in recurrence-prone migraine patients. Naratriptan International Recurrence Study Group.	2000 Aug	10972634
Are triptans with enhanced lipophilicity used for the acute treatment of migraine associated with an increased consulting rate for depressive illness?	2000 Oct	11167903
Looking forward: the expanding utility of sumatriptan and naratriptan.	2001	11678821
Building on the sumatriptan experience: the development of naratriptan.	2001	11678820
[Current topics: expectation for new triptans].	2001 Apr 10	11391915
Modeling and stimulation for clinical trial design involving a categorical response: a phase II case study with naratriptan.	2001 Aug	11587494
Naratriptan prophylactic treatment in cluster headache.	2001 Feb	11298668
A systematic review of the use of triptans in acute migraine.	2001 Feb	11252291
Pharmacokinetics of naratriptan in adolescent subjects with a history of migraine.	2001 Feb	11210397
Modulation of neuronal activity in the nucleus raphé magnus by the 5-HT(1)-receptor agonist naratriptan in rat.	2001 Feb 15	11207394
Acute treatment of migraine and the role of triptans.	2001 Mar	11898508
Donitriptan (Pierre Fabre).	2001 Mar	11575714
Advances in pharmacological treatment of migraine.	2001 Oct	11772289
Patient satisfaction with rizatriptan versus other triptans: direct head-to-head comparisons.	2001 Oct	11695077
Comparison of rizatriptan and other triptans on stringent measures of efficacy.	2001 Oct 23	11673575
Rizatriptan: an update of its use in the management of migraine.	2002	12093318
Selegiline: a second look. Six years later: too risky in Parkinson's disease.	2002 Aug	12199263
Comparison of triptan tablet consumption per attack: a prospective study of migraineurs in Spain.	2002 Feb	12005301
Health needs, drug registration and control in less developed countries--the Peruvian case.	2002 Jan-Feb	11998553
Pharmacological treatments for acute migraine: quantitative systematic review.	2002 Jun	12044621
Agonist-directed trafficking explaining the difference between response pattern of naratriptan and sumatriptan in rabbit common carotid artery.	2002 May	12010764
Validation of the Patient Perception of Migraine Questionnaire.	2002 Sep-Oct	12201859
Newer formulations of the triptans: advances in migraine management.	2003	14524731
Migraine headache.	2003 Dec	15555160
Out-patient detoxification in chronic migraine: comparison of strategies.	2003 Dec	14984232
Comparative efficacy of eletriptan and zolmitriptan in the acute treatment of migraine.	2003 Dec	14984226
[Early, but not unnecessarily frequent administration. What is proper timing for triptan drugs?].	2003 Jan 16	12638444
Eletriptan metabolism by human hepatic CYP450 enzymes and transport by human P-glycoprotein.	2003 Jul	12814962
S+ -flurbiprofen but not 5-HT1 agonists suppress basal and stimulated CGRP and PGE2 release from isolated rat dura mater.	2003 Jun	12791437
Safety profile of the triptans.	2003 Mar	12904112
Comparative efficacy of eletriptan vs. naratriptan in the acute treatment of migraine.	2003 Nov	14616928
Effects of naratriptan versus naproxen on daily functioning in the acute treatment of migraine: a randomized, double-blind, double-dummy, crossover study.	2003 Sep	12940805
Migraine: diagnosis and management.	2003 Sep-Oct	14511196
[Treatment of migraine].	2004	15484860
[Recent progress in therapy for migraine headache].	2004 Feb 10	15007953
The 5-hydroxytryptamine1B/1D/1F receptor agonists eletriptan and naratriptan inhibit trigeminovascular input to the nucleus tractus solitarius in the cat.	2004 Feb 13	14725972
The sumatriptan/naratriptan aggregated patient (SNAP) database: aggregation, validation and application.	2004 Jul	15196301
Migraine headache.	2004 Jun	15652076
Triptans and CNS side-effects: pharmacokinetic and metabolic mechanisms.	2004 Jun	15154851
Colonic ischemia associated with naratriptan use.	2004 Oct	15365406
[Meta-analysis of triptan treatment in migraine].	2004 Sep	15552863
Correlation between lipophilicity and triptan outcomes.	2005 Jan	15663606
The use of multiattribute decision models in evaluating triptan treatment options in migraine.	2005 Sep	15761676

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

Name

Type

Language

NARATRIPTAN

Official 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

NARAMIG

Brand 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