Frovatriptan Succinate

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C14H17N3O.C4H6O4.H2O
Molecular Weight	379.4076
Optical Activity	( + )
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.OC(=O)CCC(O)=O.CN[C@@H]1CCC2=C(C1)C3=C(N2)C=CC(=C3)C(N)=O

InChI

InChIKey=CUETXFMONOSVJA-KLQYNRQASA-N

InChI=1S/C14H17N3O.C4H6O4.H2O/c1-16-9-3-5-13-11(7-9)10-6-8(14(15)18)2-4-12(10)17-13;5-3(6)1-2-4(7)8;/h2,4,6,9,16-17H,3,5,7H2,1H3,(H2,15,18);1-2H2,(H,5,6)(H,7,8);1H2/t9-;;/m1../s1

HIDE SMILES / InChI

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

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

Molecular Formula	C4H6O4
Molecular Weight	118.088
Charge	0
Count

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

Molecular Formula	C14H17N3O
Molecular Weight	243.3043
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021006s006s009s010lbl.pdf

Frovatriptan succinate (trade name Frova) is a selective 5-hydroxytryptamine1 (5-HT1B/1D) receptor subtype agonist, and is used for the treatment of migraine attacks with or without aura in adults. Frovatriptan has no significant effects on GABAA mediated channel activity and has no significant affinity for benzodiazepine binding sites. Frovatriptan is believed to act on extracerebral, intracranial arteries and to inhibit excessive dilation of these vessels in migraine. Serious but rare cardiac events have been reported in patients with risk factors predictive of coronary artery disease (CAD). These include coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia and ventricular fibrillation.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serotonin 1a (5-HT1a) receptor 171 Target ID: CHEMBL214 Sources: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=5618948.PN.&OS=PN/5618948&RS=PN/5618948	Agonist 2662	62.0 nM [Ki]
Serotonin 1b (5-HT1b) receptor 45 Target ID: CHEMBL1898 Sources: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=5618948.PN.&OS=PN/5618948&RS=PN/5618948	Agonist 2662	10.3 nM [Ki]
Serotonin 1d (5-HT1d) receptor 52 Target ID: CHEMBL1983 Sources: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=5618948.PN.&OS=PN/5618948&RS=PN/5618948	Agonist 2662	4.4 nM [Ki]
Serotonin 1d (5-HT1d) receptor 52 Target ID: CHEMBL1983 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021006s006s009s010lbl.pdf	Agonist 2662
Serotonin 1b (5-HT1b) receptor 45 Target ID: CHEMBL1898 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021006s006s009s010lbl.pdf	Agonist 2662

Conditions

Condition	Modality	Targets	Highest Phase	Product
Migraine with aura 11 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021006s006s009s010lbl.pdf	Primary		Approved 8360	FROVA Approved Use FROVA is indicated for the acute treatment of migraine attacks with or without aura in adults. FROVA is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine (see CONTRAINDICATIONS). The safety and effectiveness of FROVA have not been established for cluster headache, which is present in an older, predominately male, population. Launch Date 1.0051776E12
Migraine without aura 7 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021006s006s009s010lbl.pdf	Primary		Approved 8360	FROVA Approved Use FROVA is indicated for the acute treatment of migraine attacks with or without aura in adults. FROVA is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine (see CONTRAINDICATIONS). The safety and effectiveness of FROVA have not been established for cluster headache, which is present in an older, predominately male, population. Launch Date 1.0051776E12

C_max

Value	Dose	Co-administered	Analyte	Population
2.44 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25092964	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:		FROVATRIPTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
50.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25092964	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:		FROVATRIPTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
29.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25092964	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:		FROVATRIPTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
85% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021006s019lbl.pdf			FROVATRIPTAN serum	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.8 mg single, intravenous Highest studied dose Dose: 0.8 mg Route: intravenous Route: single Dose: 0.8 mg Sources: https://pubmed.ncbi.nlm.nih.gov/12028321 Page: S56	healthy, 21 - 37 n = 12 Health Status: healthy Age Group: 21 - 37 Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/12028321 Page: S56	Sources: https://pubmed.ncbi.nlm.nih.gov/12028321 Page: S56
40 mg single, oral Highest studied dose Dose: 40 mg Route: oral Route: single Dose: 40 mg Sources: https://pubmed.ncbi.nlm.nih.gov/12028321 Page: S56	healthy, 21 - 37 n = 12 Health Status: healthy Age Group: 21 - 37 Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/12028321 Page: S56	Sources: https://pubmed.ncbi.nlm.nih.gov/12028321 Page: S56
40 mg single, oral Highest studied dose Dose: 40 mg Route: oral Route: single Dose: 40 mg Sources: https://pubmed.ncbi.nlm.nih.gov/12028323 Page: S76	unhealthy, 40.4 n = 207 Health Status: unhealthy Condition: Migraine Age Group: 40.4 Sex: M+F Population Size: 207 Sources: https://pubmed.ncbi.nlm.nih.gov/12028323 Page: S76	Sources: https://pubmed.ncbi.nlm.nih.gov/12028323 Page: S76
7.5 mg 3 times / day multiple, oral Recommended Dose: 7.5 mg, 3 times / day Route: oral Route: multiple Dose: 7.5 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021006s019lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Migraine Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021006s019lbl.pdf Page: p.1	Disc. AE: Arrhythmia, Cerebral hemorrhage... Other AEs: Myocardial ischemia, Myocardial infarction... AEs leading to discontinuation/dose reduction: Arrhythmia Cerebral hemorrhage Subarachnoid hemorrhage Stroke Gastrointestinal ischemia Peripheral vasoconstriction Serotonin syndrome Other AEs: Myocardial ischemia Myocardial infarction Prinzmetal angina Chest pain Throat pain Neck pain Jaw pain Chest tightness Throat tightness Pressure Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021006s019lbl.pdf Page: p.1
7.5 mg 3 times / day multiple, oral Recommended Dose: 7.5 mg, 3 times / day Route: oral Route: multiple Dose: 7.5 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021006s019lbl.pdf Page: p.3	unhealthy Health Status: unhealthy Condition: Migraine Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021006s019lbl.pdf Page: p.3	Disc. AE: Splenic infarction, Raynaud's syndrome... AEs leading to discontinuation/dose reduction: Splenic infarction Raynaud's syndrome Blood pressure high (grade 3) Hypertensive crisis Anaphylactic reaction (grade 4-5) Anaphylactoid reaction (grade 4-5) Angioedema (grade 4-5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021006s019lbl.pdf Page: p.3

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1579 inducer 768 substrate 1709	substrate 1010	inhibitor 1837 substrate 1193

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1509 CYP2C8/9 44 CYP2C19 1463 CYP2E1 876	CYP1A2 1032	CYP1A2 689 CYP4A 14

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1673	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-006_Frova_biopharmr.pdf Page: 29, 35	no
CYP1A2 1673	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-006_Frova_biopharmr.pdf Page: 35.0	no
CYP2C19 1537	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-006_Frova_biopharmr.pdf Page: 35.0	no
CYP2C8/9 44	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-006_Frova_biopharmr.pdf Page: 35.0	no
CYP2D6 1875	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-006_Frova_biopharmr.pdf Page: 35.0	no
CYP2E1 964	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-006_Frova_biopharmr.pdf Page: 35.0	no
CYP3A4 1909	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-006_Frova_biopharmr.pdf Page: 29, 35	no
CYP3A4 1909	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-006_Frova_biopharmr.pdf Page: 35.0	no
CYP4A 33	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-006_Frova_biopharmr.pdf Page: 29, 35	no

Drug as victim

Target	Modality	Activity
CYP2C9 1010	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-006_Frova_biopharmr.pdf Page: 35.0	no
CYP2D6 1193	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-006_Frova_biopharmr.pdf Page: 35.0	no
CYP3A4 1709	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-006_Frova_biopharmr.pdf Page: 35.0	no
CYP1A2 1032	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21-006_Frova_biopharmr.pdf Page: 29.0	yes

Sourcing

Vendor/Aggregator	ID	URL
ABI Chem	AC1L2U95
AN PharmaTech	AN-5267
Alsachim	4232	http://www.alsachim.com/product-C5550-glo.bal-view.html
Angene	AGN-PC-0Q7KOZ
BLD Pharm	BD131596	http://www.bldpharm.com/products/158747-02-5.html
BOC Sciences	147009-08-3
BOC Sciences	158930-09-7
BOC Sciences	158930-17-7
Chem Scene	CS-0021309
ChemMol	44000939	http://www.chemmol.com/chemmol/44000939.html
ChemMol	49400089	http://www.chemmol.com/chemmol/49400089.html
ChemShuttle	159065
Chemieliva Pharmaceutical Co., Ltd	PBCM1202367
Compound Cloud	152943
Compound Cloud	77992
DC Chemicals	DC22890	http://www.dcchemicals.com/product_show-DC22890.html
Hangzhou APIChem Technology	AC-4258
MolPort	MolPort-046-196-805
Molnova	M12269
MuseChem	M105240	https://www.musechem.com/product/M105240.html
Norris Pharm	NSZB-A219176
NovoSeek	77992
Parchem	29025	http://www.parchem.com/chemical-supplier-distributor/Frovatriptan-019025.aspx
Selleck Chemicals	S5848
Sigma Aldrich	1286413
Sigma Aldrich	1286413\|USP
Sigma Aldrich	SML1291
Sigma Aldrich	SML1291\|SIGMA
Smolecule	S528497	http://www.smolecule.com/products/s528497
THE BioTek	bt-268779	https://www.thebiotek.com/product/inhibitors/bt-268779
THE BioTek	bt-406286	https://www.thebiotek.com/product/others/bt-406286
Toronto Research Chemicals	M198100
Wonderchem	WD05AWA
Wonderchem	WD05AWB
ZINC	ZINC000000018635	http://zinc15.docking.org/substances/ZINC000000018635
eMolecules	225791104
eMolecules	300452900
eMolecules	45916583
eMolecules	48667526
eMolecules	76760210
eNovation Chemicals	D380881

PubMed

Title	Date	PubMed
Frovatriptan: pharmacological differences and clinical results.	2001	12463282
Pharmacokinetics and pharmacodynamics of the triptan antimigraine agents: a comparative review.	2001	11327198
Establishing a standard of speed for assessing the efficacy of the serotonin(1B/1D) agonists (triptans).	2001 Jul	11448293
Acute treatment of migraine and the role of triptans.	2001 Mar	11898508
Comparative effects of frovatriptan and sumatriptan on coronary and internal carotid vascular haemodynamics in conscious dogs.	2001 Mar	11226138
Spotlight on rizatriptan in migraine.	2002	12269863
Rizatriptan: an update of its use in the management of migraine.	2002	12093318
Tolerability and safety of frovatriptan with short- and long-term use for treatment of migraine and in comparison with sumatriptan.	2002 Apr	12028325
Clinical pharmacokinetics of frovatriptan.	2002 Apr	12028321
[Migraine has many faces. Success in differential diagnosis].	2002 Aug 8	12422737
[Treatment of migraine in patients with hypertension and ischemic heart disease].	2002 Jan 20	12122940
Mechanisms of action of the 5-HT1B/1D receptor agonists.	2002 Jul	12117355
Gateways to clinical trials.	2002 Jul-Aug	12224444
Gateways to Clinical Trials. June 2002.	2002 Jun	12168506
Gateways to clinical trials.	2002 Nov	12616707
Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials.	2002 Oct	12383060
New medications show promise for migraine sufferers.	2002 Oct	12382492
Frovatriptan: a selective type 1B/1D serotonin receptor agonist for the treatment of migraine headache.	2002 Sep	12582449
Frovatriptan Vernalis.	2002 Sep	12498015
Newer formulations of the triptans: advances in migraine management.	2003	14524731
Migraine headache recurrence: relationship to clinical, pharmacological, and pharmacokinetic properties of triptans.	2003 Apr	12656709
New drugs 2003, part I.	2003 Feb	12582288
[Also keeps long migraine attacks in check. A new triptan].	2003 Feb 6	12619371
[Migraine therapy. new specific triptan frovatriptan--long acting].	2003 Jan	12638532
Frovatriptan: a review.	2003 Jan	12517245
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
Gateways to clinical trials.	2003 Jun	12851663
Safety profile of the triptans.	2003 Mar	12904112
Gateways to clinical trials.	2004 Apr	15148527
Gateways to clinical trials.	2004 Jun	15319815
Pharmacokinetics of frovatriptan in adolescent migraineurs.	2004 Oct	15342617
Gateways to clinical trials.	2004 Sep	15538546
Randomized, placebo-controlled comparison of early use of frovatriptan in a migraine attack versus dosing after the headache has become moderate or severe.	2004 Sep	15383196
Efficacy and tolerability of frovatriptan in acute migraine treatment: systematic review of randomized controlled trials.	2005 Dec	16336284
Evidence for 5-HT2B and 5-HT7 receptor-mediated relaxation in pulmonary arteries of weaned pigs.	2005 Jan	15726452
Gateways to clinical trials.	2005 Mar	15834466
The use of multiattribute decision models in evaluating triptan treatment options in migraine.	2005 Sep	15761676
Clinical review: percutaneous dilatational tracheostomy.	2006 Feb	16356203
Tailoring management strategies for the patient with menstrual migraine: focus on prevention and treatment.	2006 Oct	17044843
Chiral separation of Frovatriptan isomers by HPLC using amylose based chiral stationary phase.	2007 Feb 1	16962393
Latest pain relief a combination of new and old.	2007 Jan	17198336
New pain management options: drugs.	2007 Jan	17198138
In silico prediction of pregnane X receptor activators by machine learning approaches.	2007 Jan	17003167
Times to pain relief and pain freedom with rizatriptan 10 mg and other oral triptans.	2007 Jul	17537184
Frova intubating catheter position can be determined with aspirating oesophageal detection device.	2007 Jun	17564685
Menstrually related migraine: breaking the cycle in your clinical practice.	2007 Oct	17977161
Frovatriptan vs. transdermal oestrogens or naproxen sodium for the prophylaxis of menstrual migraine.	2007 Oct	17955167
Acute treatment and prevention of menstrually related migraine headache: evidence-based review.	2008 Apr 22	18427072
Evaluation of clinical effectiveness of the Frova single-use tracheal tube introducer.	2008 Feb	18211451

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose is a single tablet of FROVA (frovatriptan 2.5 mg) taken orally with fluids. If the headache recurs after initial relief, a second tablet may be taken, providing there is an interval of at least 2 hours between doses. The total daily dose of frovatriptan should not exceed 3 tablets (3 x 2.5 mg per day). The safety of treating an average of more than 4 migraine attacks in a 30-day period has not been established.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Wed Jul 05 23:26:09 UTC 2023` Edited by `admin` on `Wed Jul 05 23:26:09 UTC 2023`
Record UNII	D28J6W18HY
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

Frovatriptan Succinate

Official Name

English

Frovatriptan succinate monohydrate

Common Name

English

SB 209509-AX

Code

English

SB 209509 AX

Code

English

FROVA

Code

English

MIGUARD

Brand Name

English

FROVELAN

Brand Name

English

(+)-(R)-2,3,4,9-TETRAHYDRO-3-(METHYLAMINO)-1H-CARBAZOLE-6-CARBOXAMIDE BUTANEDIOATE (1:1), MONOHYDRATE

Systematic Name

English

SB-209509-AX

Code

English

FROVATRIPTAN SUCCINATE [USP-RS]

Common Name

English

FROVATRIPTAN SUCCINATE MONOHYDRATE [MI]

Common Name

English

FROVATRIPTAN SUCCINATE [MART.]

Common Name

English

VML 251

Code

English

(+)-(R)-5,6,7,8-TETRAHYDRO-6-(METHYLAMINO)CARBAZOLE-3-CARBOXAMIDE SUCCINATE (1:1), MONOHYDRATE

Systematic Name

English

FROVATRIPTAN SUCCINATE [USAN]

Common Name

English

SB-209509AX

Code

English

MIGARD

Brand Name

English

FROVATRIPTAN SUCCINATE HYDRATE

Common Name

English

BUTANEDIOIC ACID, COMPD. WITH (R)-2,3,4,9-TETRAHYDRO-3-(METHYLAMINO)-1H-CARBAZOLE-6-CARBOXAMIDE (1:1), MONOHYDRATE

Systematic Name

English

Frovatriptan succinate monohydrate [WHO-DD]

Common Name

English

VML-251

Code

English

FROVATRIPTAN SUCCINATE [ORANGE BOOK]

Common Name

English

NSC-760422

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C47794