Solriamfetol

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C10H14N2O2
Molecular Weight	194.2304
Optical Activity	( + )
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

N[C@@H](COC(N)=O)CC1=CC=CC=C1

InChI

InChIKey=UCTRAOBQFUDCSR-SECBINFHSA-N

InChI=1S/C10H14N2O2/c11-9(7-14-10(12)13)6-8-4-2-1-3-5-8/h1-5,9H,6-7,11H2,(H2,12,13)/t9-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://adisinsight.springer.com/drugs/800030225 | http://www.ajudaily.com/view/20190321120410966 | https://www.neurologylive.com/clinical-focus/solriamfetol-fda-approval-excessive-daytime-sleepiness-narcolepsy-obstructive-sleep-apnea | https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211230s000lbl.pdf

ADX-N05, originally discovered by SK Holdings, is a selective dopamine and norepinephrine reuptake inhibitor (DNRI). ADX-N05 (Solriamfetol, sold under the brand name Sunosi) is approved in the US and is under regulatory review in the EU to improve wakefulness in adult patients with hypersomnia associated with narcolepsy or obstructive sleep apnoea.The US FDA has approved solriamfetol (Sunosi, Jazz Pharmaceuticals) for the treatment of excessive daytime sleepiness in adults with narcolepsy or obstructive sleep apnea.The dual-acting dopamine and norepinephrine reuptake inhibitor is approved for narcolepsy in once-daily 75 mg and 150 mg doses, and in obstructive sleep apnea in once-daily 37.5 mg, 75 mg, and 150 mg doses.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dopamine transporter 180 Target ID: CHEMBL238 Sources: https://www.ncbi.nlm.nih.gov/pubmed/29891587	Inhibitor 8297		2.9 µM [IC50]
Norepinephrine transporter 191 Target ID: CHEMBL222 Sources: https://www.ncbi.nlm.nih.gov/pubmed/29891587	Inhibitor 8297		4.4 µM [IC50]

C_max

Value	Dose	Co-administered	Analyte	Population
499 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30865315/	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:		SOLRIAMFETOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
5273 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30865315/	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:		SOLRIAMFETOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30865315/	75 mg single, oral dose: 75 mg route of administration: Oral experiment type: SINGLE co-administered:		SOLRIAMFETOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
112.5 mg 1 times / day steady, oral (mean) Recommended Dose: 112.5 mg, 1 times / day Route: oral Route: steady Dose: 112.5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211230s000lbl.pdf	unhealthy, 18 to 75 years n = 161 Health Status: unhealthy Condition: narcolepsy Age Group: 18 to 75 years Sex: M+F Population Size: 161 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211230s000lbl.pdf	Other AEs: Decreased appetite, Insomnia... Other AEs: Decreased appetite (9%) Insomnia (5%) Anxiety (6%) Headache (16%) Palpitations (2%) Nausea (7%) Dry mouth (4%) Constipation (3%) Agitation (<2%) Bruxism (<2%) Irritability (<2%) Cough (<2%) Hyperhidrosis (<2%) Feeling jittery (<2%) Thirst (<2%) Chest discomfort (<2%) Chest pain (<2%) Weight decreased (<2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211230s000lbl.pdf
150 mg 1 times / day steady, oral (mean) Recommended Dose: 150 mg, 1 times / day Route: oral Route: steady Dose: 150 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211230s000lbl.pdf	unhealthy, 18 to 75 years n = 218 Health Status: unhealthy Condition: narcolepsy \| obstructive sleep apnea Age Group: 18 to 75 years Sex: M+F Population Size: 218 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211230s000lbl.pdf	Disc. AE: Anxiety, Palpitations... Other AEs: Headache, Nausea... AEs leading to discontinuation/dose reduction: Anxiety (0.5%) Palpitations (0.5%) Restlessness (0.5%) Other AEs: Headache (13%) Nausea (9%) Decreased appetite (8%) Anxiety (7%) Dry mouth (4%) Diarrhea (5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211230s000lbl.pdf
37.5 mg 1 times / day steady, oral (mean) Recommended Dose: 37.5 mg, 1 times / day Route: oral Route: steady Dose: 37.5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211230s000lbl.pdf	unhealthy, 18 to 75 years n = 58 Health Status: unhealthy Condition: obstructive sleep apnea Age Group: 18 to 75 years Sex: M+F Population Size: 58 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211230s000lbl.pdf	Other AEs: Headache, Nausea... Other AEs: Headache (7%) Nausea (7%) Decreased appetite (2%) Anxiety (2%) Dry mouth (2%) Diarrhea (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211230s000lbl.pdf
75 mg 1 times / day steady, oral (mean) Recommended Dose: 75 mg, 1 times / day Route: oral Route: steady Dose: 75 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211230s000lbl.pdf	unhealthy, 18 to 75 years n = 120 Health Status: unhealthy Condition: narcolepsy \| obstructive sleep apnea Age Group: 18 to 75 years Sex: M+F Population Size: 120 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211230s000lbl.pdf	Other AEs: Headache, Nausea... Other AEs: Headache (9%) Nausea (5%) Decreased appetite (7%) Anxiety (3%) Dry mouth (3%) Diarrhea (4%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211230s000lbl.pdf
87.5 mg 1 times / day steady, oral (mean) Recommended Dose: 87.5 mg, 1 times / day Route: oral Route: steady Dose: 87.5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211230s000lbl.pdf	unhealthy, 18 to 75 years n = 235 Health Status: unhealthy Condition: obstructive sleep apnea Age Group: 18 to 75 years Sex: M+F Population Size: 235 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211230s000lbl.pdf	Other AEs: Decreased appetite, Anxiety... Other AEs: Decreased appetite (6%) Anxiety (4%) Irritability (3%) Dizziness (2%) Palpitations (3%) Nausea (8%) Diarrhea (4%) Abdominal pain (3%) Dry mouth (3%) Feeling jittery (3%) Chest discomfort (2%) Hyperhidrosis (2%) Bruxism (<2%) Restlessness (<2%) Disturbance in attention (<2%) Tremor (<2%) Cough (<2%) Dyspnea (<2%) Constipation (<2%) Vomiting (<2%) Weight decreased (<2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211230s000lbl.pdf
87.5 mg 1 times / day steady, oral (mean) Recommended Dose: 87.5 mg, 1 times / day Route: oral Route: steady Dose: 87.5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211230s000lbl.pdf	unhealthy, 18 to 75 years n = 396 Health Status: unhealthy Condition: narcolepsy \| obstructive sleep apnea Age Group: 18 to 75 years Sex: M+F Population Size: 396 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211230s000lbl.pdf	Other AEs: Blood pressure systolic increased, Blood pressure diastolic increased... Other AEs: Blood pressure systolic increased Blood pressure diastolic increased Heart rate increased Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211230s000lbl.pdf
300 mg 1 times / day single, oral Studied dose Dose: 300 mg, 1 times / day Route: oral Route: single Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30598342/	healthy, 19 to 54 years n = 32 Health Status: healthy Age Group: 19 to 54 years Sex: M+F Population Size: 32 Sources: https://pubmed.ncbi.nlm.nih.gov/30598342/	Other AEs: Insomnia, Headache... Other AEs: Insomnia (grade 1, 21.9%) Headache (grade 1, 15.6%) Hypervigilance (grade 1, 9.4%) Decreased appetite (grade 1, 9.4%) Nausea (grade 1, 9.4%) Insomnia (grade 1, 21.9%) Headache (grade 1, 12.5%) Hypervigilance (grade 1, 12.5%) Decreased appetite (grade 1, 9.4%) Nausea (grade 1, 6.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/30598342/
1200 mg 1 times / day single, oral Highest studied dose Dose: 1200 mg, 1 times / day Route: oral Route: single Dose: 1200 mg, 1 times / day Sources: https://www.ema.europa.eu/en/documents/assessment-report/sunosi-epar-public-assessment-report_en.pdf https://pubmed.ncbi.nlm.nih.gov/30269642/	healthy, mean age 29.3 years n = 42 Health Status: healthy Age Group: mean age 29.3 years Sex: M Population Size: 42 Sources: https://www.ema.europa.eu/en/documents/assessment-report/sunosi-epar-public-assessment-report_en.pdf https://pubmed.ncbi.nlm.nih.gov/30269642/	Disc. AE: Blood pressure increased, Nervousness... Other AEs: Hypervigilance, Elevated mood... AEs leading to discontinuation/dose reduction: Blood pressure increased (grade 1, 2.4%) Nervousness (grade 1, 2.4%) Other AEs: Hypervigilance (42.9%) Elevated mood (23.8%) Dry mouth (21.4%) Nausea (21.4%) Feeling of relaxation (19%) Decreased appetite (19%) Hyperhidrosis (19%) Insomnia (16.7%) Headache (14.3%) Restlessness (14.3%) Palpitations (11.9%) Paresthesia (7.1%) Sources: https://www.ema.europa.eu/en/documents/assessment-report/sunosi-epar-public-assessment-report_en.pdf https://pubmed.ncbi.nlm.nih.gov/30269642/
150 mg 1 times / day multiple, oral (mean) Studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://www.ema.europa.eu/en/documents/assessment-report/sunosi-epar-public-assessment-report_en.pdf	unhealthy n = 417 Health Status: unhealthy Condition: narcolepsy \| obstructive sleep apnea Sex: M+F Population Size: 417 Sources: https://www.ema.europa.eu/en/documents/assessment-report/sunosi-epar-public-assessment-report_en.pdf	Disc. AE: Blood pressure increased, Hypertension... AEs leading to discontinuation/dose reduction: Blood pressure increased (0.48%) Hypertension (0.24%) Sources: https://www.ema.europa.eu/en/documents/assessment-report/sunosi-epar-public-assessment-report_en.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882 CYP3A4/5 278 UGT 35 P-gp 1461 BCRP 699 OATP1B1 788 OATP1B3 706 OAT1 599 OAT3 642 OCT1 512 MATE2 263 OCTN1 29 OCTN2 66 OCT2 647 MATE1 306 UGT1A 3 UGT2B7 146	P-gp 1537 BCRP 561 OATP1B1 406 OATP1B3 350 OAT1 326 OAT3 339	CYP1A2 701 CYP2B6 547 CYP3A4/5 124 UGT 29

Drug as perpetrator

Target	Modality	Activity
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP3A4/5 335	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
OCTN1 29	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
OCTN2 71	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
UGT 59	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
UGT 59	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
UGT1A 5	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000PharmR.pdf#page=30 Page: 30.0	no
UGT2B7 157	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000PharmR.pdf#page=30 Page: 30.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	weak [IC50 146 uM]
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	weak [IC50 211 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000PharmR.pdf#page=30 Page: 30.0	weak [IC50 360 uM]

Drug as victim

Target	Modality	Activity
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000ClinPharmR.pdf#page=9 Page: 9.0	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211230Orig1Orig2s000PharmR.pdf#page=20 Page: 20.0

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P01C3BA
A2B Chem	AW42982
AA Blocks	AA01C2RU
AChemBlock	Q69522
Chem Scene	CS-0031486	http://www.chemscene.com/178429-62-4.html
ChemShuttle	139041
Chemspace	CSSB00041015464	https://chem-space.com/CSSB00041015464
Enamine	BBV-44122269
Enamine	BBV-77772338
Enamine	EN300-253107
Hairui	R2CQ017
KeyOrganics	CS-2577
MedChem Express	HY-109043	https://www.medchemexpress.com/solriamfetol.html
MolPort	MolPort-039-241-646
MolPort	MolPort-046-793-373
MolPort	MolPort-047-156-022
Molnova	M12688
MuseChem	I009552
Smolecule	S543563	http://www.smolecule.com/products/s543563
Smolecule	S727641	https://www.smolecule.com/products/s727641
THE BioTek	bt-284158	https://www.thebiotek.com/product/inhibitors/bt-284158
THE BioTek	bt-386716	https://www.thebiotek.com/product/others/bt-386716
Toronto Research Chemicals	S676775
ZINC	ZINC000034278783	http://zinc15.docking.org/substances/ZINC000034278783
eMolecules	222563444
eMolecules	303230315
eMolecules	67911099
mcule	MCULE-3233675360

PubMed

Title	Date	PubMed

Sample Use Guides

In Vivo Use Guide

The dual-acting dopamine and norepinephrine reuptake inhibitor is approved for narcolepsy in once-daily 75 mg and 150 mg doses, and in obstructive sleep apnea in once-daily 37.5 mg, 75 mg, and 150 mg doses.

Route of Administration: Oral

In Vitro Use Guide

Solriamfetol binds to the dopamine transporter and norepinephrine transporter with low affinity (Ki=14.2 uM and 3.7 uM, respectively), and inhibits the reuptake of dopamine and norepinephrine with low potency (IC50 =2.9 uM and 4.4 uM, respectively). Solriamfetol has no appreciable binding affinity for the serotonin transporter (Ki=81.5 uM) and does not inhibit serotonin reuptake (IC50 > 100 uM).

Name

Type

Language

Solriamfetol

Official Name

English

(2R)-2-Amino-3-phenylpropyl carbamate

Systematic Name

English

Solriamfetol [WHO-DD]

Common Name

English

SOLRIAMFETOL [ORANGE BOOK]

Common Name

English

YKP-10A

Code

English

R-228060

Code

English

SUNOSI

Brand Name

English

Benzenepropanol, β-amino-, 1-carbamate, (βR)-

Systematic Name

English

JZP-110

Code

English

solriamfetol [INN]

Common Name

English

Benzenepropanol, β-amino-, carbamate (ester), (βR)-

Systematic Name

English

ADX-N-05

Code

English

SKL-N-05

Code

English

SOLRIAMFETOL [USAN]

Common Name

English

SOLRIAMFETOL [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C78272