ALMOTRIPTAN MALATE

Details

Stereochemistry	RACEMIC
Molecular Formula	C17H25N3O2S.C4H6O5
Molecular Weight	469.552
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0
Stereo Comments	MALATE

SHOW SMILES / InChI

Structure Search

SMILES

OC(CC(O)=O)C(O)=O.CN(C)CCC1=CNC2=CC=C(CS(=O)(=O)N3CCCC3)C=C12

InChI

InChIKey=QHATUKWEVNMHRY-UHFFFAOYSA-N

InChI=1S/C17H25N3O2S.C4H6O5/c1-19(2)10-7-15-12-18-17-6-5-14(11-16(15)17)13-23(21,22)20-8-3-4-9-20;5-2(4(8)9)1-3(6)7/h5-6,11-12,18H,3-4,7-10,13H2,1-2H3;2,5H,1H2,(H,6,7)(H,8,9)

HIDE SMILES / InChI

Molecular Formula	C4H6O5
Molecular Weight	134.0874
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

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.accessdata.fda.gov/drugsatfda_docs/label/2009/021001s010s011lbl.pdf | https://www.drugs.com/cdi/almotriptan.html

Almotriptan is a triptan drug for the treatment of migraine headaches. Almotriptan is marketed under the trade name Axert. Almotriptan is used for treating acute migraine headaches with or without aura (eg, dark spots, flashing lights, wavy lines). Almotriptan binds with high affinity to 5-HT1D, 5-HT1B, and 5-HT1F receptors. Almotriptan has weak affinity for 5-HT1A and 5-HT7 receptors, but has no significant affinity or pharmacological activity at 5-HT2, 5-HT3, 5-HT4, 5-HT6; alpha or beta adrenergic; adenosine (A1, A2); angiotensin (AT1, AT2); dopamine (D1, D2); endothelin (ETA, ETB); or tachykinin (NK1, NK2, NK3) binding sites.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotonin 1b (5-HT1b) receptor 43 Target ID: CHEMBL1898 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021001s008s009lbl.pdf	Agonist 2637
Serotonin 1d (5-HT1d) receptor 52 Target ID: CHEMBL1983 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021001s010s011lbl.pdf	Agonist 2637
Serotonin 1f (5-HT1f) receptor 15 Target ID: CHEMBL1805 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021001s010s011lbl.pdf	Agonist 2637

Conditions

Condition	Modality	Targets	Highest Phase	Product
Migraine 103 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021001s010s011lbl.pdf	Primary		Approved 8307	AXERT Approved Use Almotriptan tablets, USP are a 5HT1B/1D receptor agonist (triptan) indicated for: •Acute treatment of migraine attacks in adults with a history of migraine with or without aura (1.1) •Acute treatment of migraine headache pain in adolescents age 12 to 17 years with a history of migraine with or without aura, and who have migraine attacks usually lasting 4 hours or more (1.1) Important Limitations: •Use only after a clear diagnosis of migraine has been established (1.2) •In adolescents age 12 to 17 years, efficacy of almotriptan tablets on migraine-associated symptoms was not established (1.2) •Not intended for the prophylactic therapy of migraine (1.2) •Not indicated for the treatment of cluster headache (1.2) 1.1 Acute Treatment of Migraine Attacks Adults Almotriptan tablets, USP are indicated for the acute treatment of migraine attacks in patients with a history of migraine with or without aura. Adolescents Age 12 to 17 Years Almotriptan tablets are indicated for the acute treatment of migraine headache pain in patients with a history of migraine attacks with or without aura usually lasting 4 hours or more (when untreated). 1.2 Important Limitations Almotriptan tablets should only be used where a clear diagnosis of migraine has been established. If a patient has no response for the first migraine attack treated with almotriptan tablets, the diagnosis of migraine should be reconsidered before almotriptan tablets are administered to treat any subsequent attacks. In adolescents age 12 to 17 years, efficacy of almotriptan tablets on migraine-associated symptoms (nausea, photophobia, and phonophobia) was not established. Almotriptan tablets are not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine [see Contraindications (4.7) Launch Date 9.8919357E11

C_max

Value	Dose	Co-administered	Analyte	Population
52.6 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/12723463	12.5 mg single, oral dose: 12.5 mg route of administration: Oral experiment type: SINGLE co-administered:		ALMOTRIPTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
312 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/12723463	12.5 mg single, oral dose: 12.5 mg route of administration: Oral experiment type: SINGLE co-administered:		ALMOTRIPTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
6.1 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/12723463	12.5 mg single, oral dose: 12.5 mg route of administration: Oral experiment type: SINGLE co-administered:		ALMOTRIPTAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3.5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021001s015lbl.pdf	unknown, oral		ALMOTRIPTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
65% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/021001s015lbl.pdf	unknown, oral		ALMOTRIPTAN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
3 mg single, intravenous Dose: 3 mg Route: intravenous Route: single Dose: 3 mg Sources: https://pubmed.ncbi.nlm.nih.gov/12463724	healthy, 19-33 years n = 24 Health Status: healthy Age Group: 19-33 years Sex: M Population Size: 24 Sources: https://pubmed.ncbi.nlm.nih.gov/12463724	Sources: https://pubmed.ncbi.nlm.nih.gov/12463724
10 mg single, subcutaneous Highest studied dose Dose: 10 mg Route: subcutaneous Route: single Dose: 10 mg Sources: https://pubmed.ncbi.nlm.nih.gov/11768838	unhealthy, 42 years (range: 18-72 years) n = 31 Health Status: unhealthy Condition: acute migraine Age Group: 42 years (range: 18-72 years) Sex: M+F Population Size: 31 Sources: https://pubmed.ncbi.nlm.nih.gov/11768838	Sources: https://pubmed.ncbi.nlm.nih.gov/11768838
12.5 mg multiple, oral Recommended Dose: 12.5 mg Route: oral Route: multiple Dose: 12.5 mg Sources: https://pubmed.ncbi.nlm.nih.gov/12005273	unhealthy, 42 years (range: 18-72 years) n = 582 Health Status: unhealthy Condition: acute migraine Age Group: 42 years (range: 18-72 years) Sex: M+F Population Size: 582 Sources: https://pubmed.ncbi.nlm.nih.gov/12005273	Disc. AE: Chest pain, Electrocardiogram QTc interval prolonged... AEs leading to discontinuation/dose reduction: Chest pain (0.9%) Electrocardiogram QTc interval prolonged (0.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/12005273
100 mg multiple, oral Highest studied dose Dose: 100 mg Route: oral Route: multiple Dose: 100 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21001_Axert_prntlbl.pdf	unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21001_Axert_prntlbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21001_Axert_prntlbl.pdf
200 mg single, oral Highest studied dose Dose: 200 mg Route: oral Route: single Dose: 200 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21001_Axert_prntlbl.pdf	healthy, adult n = 6 Health Status: healthy Age Group: adult Population Size: 6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21001_Axert_prntlbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21001_Axert_prntlbl.pdf

AEs

AE	Significance	Dose	Population
Electrocardiogram QTc interval prolonged	0.7% Disc. AE	12.5 mg multiple, oral Recommended Dose: 12.5 mg Route: oral Route: multiple Dose: 12.5 mg Sources: https://pubmed.ncbi.nlm.nih.gov/12005273	unhealthy, 42 years (range: 18-72 years) n = 582 Health Status: unhealthy Condition: acute migraine Age Group: 42 years (range: 18-72 years) Sex: M+F Population Size: 582 Sources: https://pubmed.ncbi.nlm.nih.gov/12005273
Chest pain	0.9% Disc. AE	12.5 mg multiple, oral Recommended Dose: 12.5 mg Route: oral Route: multiple Dose: 12.5 mg Sources: https://pubmed.ncbi.nlm.nih.gov/12005273	unhealthy, 42 years (range: 18-72 years) n = 582 Health Status: unhealthy Condition: acute migraine Age Group: 42 years (range: 18-72 years) Sex: M+F Population Size: 582 Sources: https://pubmed.ncbi.nlm.nih.gov/12005273

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1670	inhibitor 1695	substrate 1168 inhibitor 1789

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1463 CYP2A6 670 CYP2B6 770 CYP2C19 1410 CYP2E1 846 CYP3A4/5 261 CYP4A9/11 34	FMO3 65 CYP3A4/5 82 CYP1A2 1013 CYP2C8 670 CYP2C19 955

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1620	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21001_Axert_pharmr_P1.pdf Page: 49.0	no
CYP2A6 702	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21001_Axert_pharmr_P1.pdf Page: 49.0	no
CYP2B6 946	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21001_Axert_pharmr_P1.pdf Page: 49.0	no
CYP2C19 1484	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21001_Axert_pharmr_P1.pdf Page: 49.0	no
CYP2C9 1747	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21001_Axert_pharmr_P1.pdf Page: 49.0	no
CYP2E1 929	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21001_Axert_pharmr_P1.pdf Page: 49.0	no
CYP3A4/5 314	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21001_Axert_pharmr_P1.pdf Page: 49.0	no
CYP4A9/11 34	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21001_Axert_pharmr_P1.pdf Page: 49.0	no
CYP2D6 1826	inhibitor 3185 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21001_Axert_pharmr_P1.pdf Page: 49.0	weak [Ki 87 uM]

Drug as victim

Target	Modality	Activity
CYP1A2 1013	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21001_Axert_pharmr_P1.pdf Page: 27.0	yes
CYP2C19 955	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21001_Axert_pharmr_P1.pdf Page: 27.0	yes
CYP2C8 670	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21001_Axert_pharmr_P1.pdf Page: 27.0	yes
CYP2D6 1168	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21001_Axert_pharmr_P1.pdf Page: 27.0	yes
CYP3A4 1670	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21001_Axert_pharmr_P1.pdf Page: 27, 49	yes
CYP3A4/5 82	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21001_Axert_pharmr_P1.pdf Page: 27.0	yes
FMO3 65	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21001_Axert_pharmr_P1.pdf Page: 27.0	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:520985	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:520985
ChemicalBook	CB7716603	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7716603
ZINC	ZINC000000018087	http://zinc15.docking.org/substances/ZINC000000018087
eMolecules	5852303	https://www.emolecules.com/cgi-bin/more?vid=5852303

PubMed

Title	Date	PubMed
Almotriptan: pharmacological differences and clinical results.	2001	12463281
Establishing a standard of speed for assessing the efficacy of the serotonin(1B/1D) agonists (triptans).	2001 Jul	11448293
Oral almotriptan vs. oral sumatriptan in the abortive treatment of migraine: a double-blind, randomized, parallel-group, optimum-dose comparison.	2001 Jun	11405809
Efficacy and tolerability of subcutaneous almotriptan for the treatment of acute migraine: a randomized, double-blind, parallel-group, dose-finding study.	2001 Nov	11768838
Oral triptans (serotonin 5-HT(1B/1D) agonists) in acute migraine treatment: a meta-analysis of 53 trials.	2001 Nov 17	11728541
Vascular effects of the new anti-migraine agent almotriptan on human cranial and peripheral arteries.	2001 Oct	11737005
Spotlight on rizatriptan in migraine.	2002	12269863
Rizatriptan: an update of its use in the management of migraine.	2002	12093318
Almotriptan: a review of its use in migraine.	2002	11817980
Use of rescue medication in trials of almotriptan versus placebo in the treatment of acute migraine.	2002 Apr	12017397
Almotriptan, a new anti-migraine agent: a review.	2002 Fall	12353056
Health outcomes evaluations: estimating the impact of almotriptan in managed care settings.	2002 Feb	11859909
Almotriptan: a review of pharmacology, clinical efficacy, and tolerability.	2002 Feb	11859907
Migraine: diagnosis, management, and new treatment options.	2002 Feb	11859906
Cost savings in migraine associated with less chest pain on new triptan therapy.	2002 Feb	11859905
Almotriptan (Axert) and frovatriptan (Frova) for migrane.	2002 Feb 18	11856954
Almotriptan increases pain-free status in patients with acute migraine treated in placebo-controlled clinical trials.	2002 Jan	11966862
Almotriptan reduces the incidence of migraine-associated symptoms: a pooled analysis.	2002 Jan	11966861
Tripstar: a comprehensive patient-based approach to compare triptans.	2002 Jan	11966860
Clinical benefits of early triptan therapy for migraine.	2002 Jan	11966859
[Treatment of migraine in patients with hypertension and ischemic heart disease].	2002 Jan 20	12122940
Cardiovascular effect of almotriptan in treated hypertensive patients.	2002 Mar	11907491
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
Current perspectives on effective migraine treatments: are small clinical differences important for patients?	2003	15071619
Newer formulations of the triptans: advances in migraine management.	2003	14524731
Gateways to clinical trials.	2003 Dec	14735233
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
A review of the clinical efficacy and tolerability of almotriptan in acute migraine.	2003 Jul	12831340
Almotriptan versus rizatriptan in patients with migraine in Spain.	2003 Jul-Aug	12890128
Safety profile of the triptans.	2003 Mar	12904112
Gateways to clinical trials. March 2003.	2003 Mar	12731460
Early intervention with almotriptan improves sustained pain-free response in acute migraine.	2003 Nov-Dec	14629242
Migraine: diagnosis and management.	2003 Sep-Oct	14511196
Clinical benefits of early triptan therapy for migraine.	2004	15595991
Clinical profile and practice experience of almotriptan.	2004	15595990
Migraine pathophysiology and its clinical implications.	2004	15595988
Almotriptan improves response rates when treatment is within 1 hour of migraine onset.	2004 Apr	15109355
Triptans and chest symptoms: the role of pulmonary vasoconstriction.	2004 Apr	15030540
A comparison of the pharmacokinetics and tolerability of the anti-migraine compound almotriptan in healthy adolescents and adults.	2004 Apr	15030538
Meta-analysis of oral triptans.	2004 Aug	15265060
Evaluating triptan usage.	2004 Feb	14756865
Validation of a general measure of treatment satisfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM), using a national panel study of chronic disease.	2004 Feb 26	14987333
Gateways to clinical trials.	2004 Jan-Feb	14988742
Patterns of use of triptans and reasons for switching them in a tertiary care migraine population.	2004 Jul-Aug	15209687
Triptans and CNS side-effects: pharmacokinetic and metabolic mechanisms.	2004 Jun	15154851
Cost considerations of acute migraine treatment.	2004 Mar	15012668
A comparison of the cost-effectiveness of almotriptan and sumatriptan in the treatment of acute migraine using a composite efficacy/tolerability end point.	2004 May-Jun	15228377
TRIPSTAR: prioritizing oral triptan treatment attributes in migraine management.	2004 Sep	15285768
Correlation between lipophilicity and triptan outcomes.	2005 Jan	15663606

Patents

Sample Use Guides

In Vivo Use Guide

Adults and adolescents age 12 to 17 years: 6.25 mg or 12.5 mg single dose; may repeat after 2 hours if headache returns; benefit of second dose in patients who have failed to respond to first dose has not been established; maximum daily dose 25 mg Patients with hepatic or severe renal impairment: 6.25 mg starting dose; maximum daily dose 12.5 mg

Route of Administration: Oral

In Vitro Use Guide

In vitro Almotriptan showed selectivity of action for migraine-related human arteries (i.e. contractile EC(50) of 30 and 700 nm for meningeal and temporal arteries, respectively), whereas the effect on arteries supplying blood to the brain was lower.

Substance Class	Chemical Created by `admin` on `Fri Dec 16 18:37:03 UTC 2022` Edited by `admin` on `Fri Dec 16 18:37:03 UTC 2022`
Record UNII	PJP312605E
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ALMOTRIPTAN MALATE

Official Name

English

LAS-31416 D,L-MALATE ACID

Code

English

ALMOTRIPTAN MALATE [ORANGE BOOK]

Common Name

English

ALMOTRIPTAN MALATE [EP MONOGRAPH]

Common Name

English

LAS-31416-D,L-MALATE-ACID

Code

English

1-(((3-(2-(DIMETHYLAMINO)ETHYL)-1H-INDOL-5-YL)METHYL)SULFONYL)PYRROLIDINE, HYDROXYBUTANEDIOATE (1:1)

Systematic Name

English

ALMOTRIPTAN MALEATE [MI]

Common Name

English

ALMOTRIPTAN MALATE [USAN]

Common Name

English

ALMOTRIPTAN MALEATE

Common Name

English

Almotriptan malate [WHO-DD]

Common Name

English

ALMOTRIPTAN D,L-HYDROGENMALATE

Common Name

English

ALMOTRIPTAN MALATE [USP-RS]

Common Name

English

1-[({3-[2-(Dimethylamino)ethyl]indol-5-yl}methyl)sulfonyl]pyrrolidine malate (1:1)

Systematic Name

English

ALMOTRIPTAN MALATE [VANDF]

Common Name

English

ALMOGRAN

Common Name

English

ALMOTRIPTAN MALATE [USP MONOGRAPH]

Common Name

English

LAS 31416 D,L-MALATE ACID

Code

English

AXERT

Brand Name

English

PNU-180638E

Code

English

ALMOTRIPTAN MALATE [MART.]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C47794