LASMIDITAN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H18F3N3O2
Molecular Weight	377.3603
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1CCC(CC1)C(=O)C2=CC=CC(NC(=O)C3=C(F)C=C(F)C=C3F)=N2

InChI

InChIKey=XEDHVZKDSYZQBF-UHFFFAOYSA-N

InChI=1S/C19H18F3N3O2/c1-25-7-5-11(6-8-25)18(26)15-3-2-4-16(23-15)24-19(27)17-13(21)9-12(20)10-14(17)22/h2-4,9-11H,5-8H2,1H3,(H,23,24,27)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20855361 | https://www.ncbi.nlm.nih.gov/mesh/67554777 | https://www.ncbi.nlm.nih.gov/pubmed/31340760

LASMIDITAN is a serotonin (5-HT) receptor agonist without vasoconstrictor activity, which selectively binds to the 5-HT(1F) receptor subtype. It is under development for the treatment of migraine.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotonin 1f (5-HT1f) receptor 15 Target ID: CHEMBL1805 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20855361	Agonist 2678		2.1 nM [Ki]

C_max

Value	Dose	Analyte	Population
322.8 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/29563831/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	LASMIDITAN serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
394.7 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/29563831/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	LASMIDITAN serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
526.15 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT03465436	400 mg single, oral dose: 400 mg route of administration: oral experiment type: single co-administered:	LASMIDITAN unknown	Homo sapiens population: healthy age: sex: food status:

AUC

Value	Dose	Analyte	Population
1892 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/29563831/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	LASMIDITAN serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
2244 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/29563831/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	LASMIDITAN serum	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
3189.08 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT03465436	400 mg single, oral dose: 400 mg route of administration: oral experiment type: single co-administered:	LASMIDITAN unknown	Homo sapiens population: healthy age: sex: food status:

Doses

Dose	Population	Adverse events
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf	unhealthy, 18-81 years n = 1265 Health Status: unhealthy Condition: migraine Age Group: 18-81 years Sex: M+F Population Size: 1265 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf	Other AEs: Dizziness, Fatigue... Other AEs: Dizziness (15%) Fatigue (5%) Paresthesia (7%) Sedation (6%) Nausea and vomiting (4%) Muscle weakness (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf	unhealthy, 18-81 years n = 1258 Health Status: unhealthy Condition: migraine Age Group: 18-81 years Sex: M+F Population Size: 1258 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf	Other AEs: Dizziness, Fatigue... Other AEs: Dizziness (17%) Fatigue (6%) Paresthesia (9%) Sedation (7%) Nausea and vomiting (4%) Muscle weakness (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf
50 mg 1 times / day steady, oral Recommended Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf	unhealthy, 18-81 years n = 654 Health Status: unhealthy Condition: migraine Age Group: 18-81 years Sex: M+F Population Size: 654 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf	Other AEs: Dizziness, Fatigue... Other AEs: Dizziness (9%) Fatigue (4%) Paresthesia (3%) Sedation (6%) Nausea and vomiting (3%) Muscle weakness (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf
120 mg 5 times / day single, oral Highest studied dose Dose: 120 mg, 5 times / day Route: oral Route: single Dose: 120 mg, 5 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000MedR.pdf	unhealthy, adults n = 1 Health Status: unhealthy Condition: migraine Age Group: adults Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000MedR.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000MedR.pdf
400 mg 1 times / day single, oral Highest studied dose Dose: 400 mg, 1 times / day Route: oral Route: single Dose: 400 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000MedR.pdf	unhealthy, adults n = 70 Health Status: unhealthy Condition: migraine Age Group: adults Sex: M+F Population Size: 70 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000MedR.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000MedR.pdf
100 mg 1 times / day steady, oral Recommended Dose: 100 mg, 1 times / day Route: oral Route: steady Dose: 100 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000MedR.pdf	unhealthy, adults n = 991 Health Status: unhealthy Condition: migraine Age Group: adults Sex: M+F Population Size: 991 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000MedR.pdf	Disc. AE: Dizziness, Light headedness... AEs leading to discontinuation/dose reduction: Dizziness (2.8%) Light headedness (2.8%) Somnolence (1.6%) Sedation (1.6%) Asthenia (0.7%) Fatigue (0.7%) Malaise (0.7%) Weakness (0.7%) Paresthesia (0.8%) Hypoaesthesia (0.8%) Nausea (0.7%) Vomiting (0.7%) Confusion (2.1%) Delirium (2.1%) Mental status changes (2.1%) Disorientation (2.1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000MedR.pdf
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000MedR.pdf	unhealthy, adults n = 1039 Health Status: unhealthy Condition: migraine Age Group: adults Sex: M+F Population Size: 1039 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000MedR.pdf	Disc. AE: Dizziness, Light headedness... Other AEs: Confusion, Delirium... AEs leading to discontinuation/dose reduction: Dizziness (4.2%) Light headedness (4.2%) Somnolence (1.2%) Sedation (1.2%) Asthenia (2.5%) Fatigue (2.5%) Malaise (2.5%) Weakness (2.5%) Paresthesia (1.8%) Hypoaesthesia (1.8%) Nausea (1.5%) Vomiting (1.5%) Confusion (1.4%) Delirium (1.4%) Mental status changes (1.4%) Disorientation (1.4%) Other AEs: Confusion (1.4%) Delirium (1.4%) Mental status changes (1.4%) Disorientation (1.4%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000MedR.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	inhibitor 1767 substrate 1037 inducer 389	inhibitor 1852 substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 BCRP 699 OCT1 512 CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882 CYP3A 214 FMO3 3 MATE1 306 MATE2 263 OCT2 647 OAT1 599 OAT3 642 OATP1B1 788 OATP1B3 706	P-gp 1537 CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2C19 991 CYP2E1 667	CYP3A 129 CYP1A2 701

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
FMO3 3	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	low
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	low
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	low
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	low
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	low
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	low
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000ClinPharmR.pdf#page=18 Page: 8, 18	low	no (co-administration study) Comment: "when administered with sumatriptan, no change in sumatriptan PK was observed; '""low potential of interactions""" Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000ClinPharmR.pdf#page=18 Page: 8, 18
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0	no
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0	no	no (co-administration study) Comment: administered with caffeine, daily dosing of lasmiditan did not alter PK of caffeine Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0	no	no (co-administration study) Comment: administered with caffeine, daily dosing of lasmiditan did not alter PK of caffeine Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0	no	no (co-administration study) Comment: administered with tolbutamide, daily dosing of lasmiditan did not alter the PK of tolbutamide. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0	no	no (co-administration study) Comment: administered with tolbutamide, daily dosing of lasmiditan did not alter the PK of tolbutamide. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0
CYP3A 298	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0	no	no (co-administration study) Comment: administered with midazolam, daily dosing of lasmiditan did not alter PK of midazolam Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0
CYP3A 298	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0	no	no (co-administration study) Comment: administered with midazolam, daily dosing of lasmiditan did not alter PK of midazolam Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000ClinPharmR.pdf#page=37 Page: 37.0	yes [IC50 85 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000ClinPharmR.pdf#page=37; https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 37, 8	yes [Ki 20.7 uM]
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000ClinPharmR.pdf#page=16 Page: 16.0	yes
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	yes
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000ClinPharmR.pdf#page=18 Page: 18.0	yes

Drug as victim

Target	Modality	Activity
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0	no
CYP2A6 543	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0	no
CYP2B6 664	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0	no
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0	no
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0	no
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0	no
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0	no
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0	no
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211280s000lbl.pdf#page=8 Page: 8.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211280Orig1s000ClinPharmR.pdf#page=18 Page: 18.0

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY113432	https://www.001chemical.com/chem/439239-90-4
AA Blocks	AA00DB3R	https://www.aablocks.com/goods/Goods/detail?id=AA00DB3R
AK Scientific, Inc. (AKSCI)	6063AB	http://www.aksci.com/item_detail.php?cat=6063AB
Aaron Chemicals	AR00DBVJ	http://www.aaronchem.com/439239-90-4
AbMole Bioscience	M10160	http://www.abmole.com/products/lasmiditan.html
AbMole Bioscience	M5214	http://www.abmole.com/products/lasmiditan.html
Achemo Scientific Limited	AC-105121	http://www.achemo.com/search/?Keyword=439239-90-4
Achemtek	0104-035885	http://www.achemtek.com/439239-90-4
Adooq BioScience	A14198	https://www.adooq.com/lasmiditan.html
Ambinter	Amb22233527	http://www.ambinter.com/reference/22233527
Angel Pharmatech	AG-11845	http://www.angelpharmatech.com/439239-90-4.html
Angene	AGN-PC-00CM98	http://www.angenechemical.com/productshow/AGN-PC-00CM98.html
ApexBio Technology	B1058	http://www.apexbt.com/lasmiditan.html
Ark Pharma Scientific Limited	A-1201	http://www.arkpharmtech.com/product/33152.html
Aurora Fine Chemicals LLC	A13.105.806	http://online.aurorafinechemicals.com/info?ID=A13.105.806
BioChemPartner	BCP04734	http://www.biochempartner.com/439239-90-4-BCP04734
BioCrick	BCC4077	http://www.biocrick.com/Lasmiditan-BCC4077.html
Boerchem	BC600589	http://www.boerchem.com/?product_43424.html
Chem Scene	CS-2032	http://www.chemscene.com/439239-90-4.html
Chemspace	CSSB00015188126	https://chem-space.com/CSSB00015188126
Clearsynth	CS-MM-09003	https://www.clearsynth.com/en/CSMM09003.html
DC Chemicals	DC7710	http://www.dcchemicals.com/product_show-Lasmiditan_COL_144_LY573144_.html
Excenen	EX-A1300	http://www.excenen.com/searchresultlist.php?id=439239-90-4
Excenen	EX-A1653	http://www.excenen.com/searchresultlist.php?id=439239-90-4
Lab Network	LN00188248	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00188248
Matrix Scientific	90054	https://www.matrixscientific.com/090054.html
MedChem Express	HY-14861	https://www.medchemexpress.com/lasmiditan.html
Molcore	MC113432	https://www.molcore.com/product/439239-90-4
Selleck Chemicals	S5064	http://www.selleckchem.com/products/lasmiditan.html
Smolecule	S532530	http://www.smolecule.com/products/s532530
Synblock Inc	SB19007	http://www.synblock.com/product/439239-90-4.html
THE BioTek	bt-272592	https://www.thebiotek.com/product/inhibitors/bt-272592
THE BioTek	bt-341446	https://www.thebiotek.com/product/others/bt-341446
abcr GmbH	AB479695	http://www.abcr.com/shop/en/AB479695
eNovation Chemicals	D501949	http://www.enovationchem.com/productDetails.asp?productID=D501949
eNovation Chemicals	Y1012792	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y1012792

PubMed

Title	Date	PubMed
Acute treatment of migraine with the selective 5-HT1F receptor agonist lasmiditan--a randomised proof-of-concept trial.	2010 Oct	20855362
Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan.	2010 Oct	20855361
Molecule of the month. Lasmiditan hydrochloride.	2010 Sep	20862397

Patents

Sample Use Guides

In Vitro Use Guide

Lasmiditan in vitro binding studies show a Ki value of 2.21 nM at the 5-HT(1F) serotonin receptor, compared with Ki values of 1043 nM and 1357 nM at the 5-HT(1B) and 5-HT(1D) receptors, respectively. Lasmiditan did not contract rabbit saphenous vein rings, a surrogate assay for human coronary artery constriction, at concentrations up to 100 uM.

Name

Type

Language

LASMIDITAN

Official Name

English

Lasmiditan [WHO-DD]

Common Name

English

2,4,6-Trifluoro-N-{6-[(1-methylpiperidine-4-yl)carbonyl]pyridin-2-yl}benzamide

Systematic Name

English

COL-144

Code

English

lasmiditan [INN]

Common Name

English

LASMIDITAN [MI]

Common Name

English

LASMIDITAN [USAN]

Common Name

English

Classification Tree Code System Code

DEA NO.

2790