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
Comparative aspects of triptans in treating migraine.	2001	12739316
Naratriptan.	2001	12463278
Sumatriptan: pharmacological basis and clinical results.	2001	12463276
An introduction to migraine: from ancient treatment to functional pharmacology and antimigraine therapy.	2002	12434581
Restoring migraine sufferers' ability to function normally: a comparison of rizatriptan and other triptans in randomized trials.	2002	12373035
Spotlight on rizatriptan in migraine.	2002	12269863
Rizatriptan: an update of its use in the management of migraine.	2002	12093318
Gateways to Clinical Trials.	2002 Apr	12087878
Selegiline: a second look. Six years later: too risky in Parkinson's disease.	2002 Aug	12199263
Triptans reduce the inflammatory response in bacterial meningitis.	2002 Aug	12172384
Naratriptan in the preventive treatment of cluster headache.	2002 Dec	12485208
Mechanisms of action of the 5-HT1B/1D receptor agonists.	2002 Jul	12117355
Gateways to Clinical Trials. June 2002.	2002 Jun	12168506
Gateways to clinical trials.	2002 Nov	12616707
[Ischemic colitis associated with naratriptan administration].	2002 Nov	12483146
Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials.	2002 Oct	12383060
Validation of the Patient Perception of Migraine Questionnaire.	2002 Sep-Oct	12201859
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
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
Meta-analysis of oral triptan therapy for migraine: number needed to treat and relative cost to achieve relief within 2 hours.	2003 Jan-Feb	14613361
Migraine: pathophysiology, pharmacology, treatment and future trends.	2003 Mar	15320857
[A descriptive analysis of naratriptan use among migraineurs in ambulatory medicine].	2003 May	12773900
Naratriptan in the preventive treatment of refractory chronic migraine: a review of 27 cases.	2003 May	12752754
Demographic and migraine characteristics of adolescents with migraine: Glaxo Wellcome clinical trials' database.	2003 May	12752749
[Highly selective beginning. Associated symptoms and side effects in retrospect].	2003 May 26	14579499
[Improved pharmacokinetics. Fast tryptan with sustained response].	2003 May 26	14579498
Managing intractable migraine with naratriptan.	2003 Oct	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 Oct	12954804
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
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
Triptans and gastric accommodation: pharmacological and therapeutic aspects.	2004 Jan	14971822
The sumatriptan/naratriptan aggregated patient (SNAP) database: aggregation, validation and application.	2004 Jul	15196301
Involvement of 5-HT1B receptors in triptan-induced contractile responses in guinea-pig isolated iliac artery.	2004 Jul	15185063
Patterns of use of triptans and reasons for switching them in a tertiary care migraine population.	2004 Jul-Aug	15209687
Migraine headache.	2004 Jun	15652076
Transformed migraine and medication overuse in a tertiary headache centre--clinical characteristics and treatment outcomes.	2004 Jun	15154858
Triptans and CNS side-effects: pharmacokinetic and metabolic mechanisms.	2004 Jun	15154851
Rizatriptan versus rizatriptan plus rofecoxib versus rizatriptan plus tolfenamic acid in the acute treatment of migraine.	2004 Jun 28	15222892
Efficacy of quality criteria to identify potentially harmful information: a cross-sectional survey of complementary and alternative medicine web sites.	2004 Jun 29	15249270
Colonic ischemia associated with naratriptan use.	2004 Oct	15365406
[Meta-analysis of triptan treatment in migraine].	2004 Sep	15552863
Activation of 5-HT(1B/1D) receptor in the periaqueductal gray inhibits nociception.	2004 Sep	15349864
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