DASOTRALINE HYDROCHLORIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C16H15Cl2N.ClH
Molecular Weight	328.664
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.N[C@@H]1CC[C@@H](C2=CC(Cl)=C(Cl)C=C2)C3=CC=CC=C13

InChI

InChIKey=YKXHIERZIRLOLD-DFIJPDEKSA-N

InChI=1S/C16H15Cl2N.ClH/c17-14-7-5-10(9-15(14)18)11-6-8-16(19)13-4-2-1-3-12(11)13;/h1-5,7,9,11,16H,6,8,19H2;1H/t11-,16+;/m0./s1

HIDE SMILES / InChI

Description
Sources: https://www.drugs.com/clinical_trials/sunovion-announces-top-line-results-studies-evaluating-dasotraline-adults-binge-eating-disorder-17524.html

Dasotraline, also known as SEP-225,289, is a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI). It has an extended half-life (47-77 hours) that supports the potential for plasma concentrations yielding a continuous therapeutic effect over the 24-hour dosing interval at steady state. Dasotraline has shown a lower potential for abuse than methylphenidate in clinical testing. Dasotraline was discovered by Sunovion Pharmaceuticals Inc. and is currently in development to evaluate its use in treating ADHD in adults and children, and BED in adults in the United States. It has not been approved by the U.S. Food and Drug Administration (FDA) for the treatment of ADHD, BED or any other disorder.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Monoamine transporter 10 Target ID: CHEMBL2363064 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25948101	Inhibitor 8297
Serotonin transporter 178 Target ID: CHEMBL313 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21680689 \| http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=biology&ligandId=8308	Inhibitor 8297	11.0 nM [IC50]
Norepinephrine transporter 191 Target ID: CHEMBL304 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21680689 \| http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=biology&ligandId=8308	Inhibitor 8297	6.0 nM [IC50]
Dopamine transporter 180 Target ID: CHEMBL338 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21680689 \| http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=biology&ligandId=8308	Inhibitor 8297	4.0 nM [IC50]
Sodium-dependent serotonin transporter 40 Target ID: P31645 Gene ID: 6532.0 Gene Symbol: SLC6A4 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/21680689	Inhibitor 8297
Sodium-dependent dopamine transporter 42 Target ID: Q01959 Gene ID: 6531.0 Gene Symbol: SLC6A3 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/21680689	Inhibitor 8297
Sodium-dependent noradrenaline transporter 38 Target ID: P23975 Gene ID: 6530.0 Gene Symbol: SLC6A2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/21680689

Conditions

Condition	Modality	Targets	Highest Phase	Product
Binge eating disorder 4 Sources: https://clinicaltrials.gov/ct2/show/NCT03107026	Primary		Phase III 656	Unknown Approved Use Unknown
Attention deficit hyperactivity disorder 68 Sources: https://clinicaltrials.gov/ct2/show/NCT02160262 https://clinicaltrials.gov/ct2/show/NCT02428088	Primary		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
14 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26794682	36 mg single, oral dose: 36 mg route of administration: Oral experiment type: SINGLE co-administered:		DASOTRALINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
740 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26794682	36 mg single, oral dose: 36 mg route of administration: Oral experiment type: SINGLE co-administered:		DASOTRALINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
36 mg single, oral Highest studied dose Dose: 36 mg Route: oral Route: single Dose: 36 mg Sources: https://pubmed.ncbi.nlm.nih.gov/26794682 Page: p.32	healthy, ADULT n = 39 Health Status: healthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 39 Sources: https://pubmed.ncbi.nlm.nih.gov/26794682 Page: p.32	Disc. AE: Ventricular tachycardia... AEs leading to discontinuation/dose reduction: Ventricular tachycardia (2.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/26794682 Page: p.32
5.5 mg 1 times / day multiple, oral (mean) Studied dose Dose: 5.5 mg, 1 times / day Route: oral Route: multiple Dose: 5.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32926604 Page: e5, sup. table 2	unhealthy, ADULT n = 155 Health Status: unhealthy Condition: eating disorder Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 155 Sources: https://pubmed.ncbi.nlm.nih.gov/32926604 Page: e5, sup. table 2	Disc. AE: Insomnia, Paranoia... AEs leading to discontinuation/dose reduction: Insomnia (grade 3, 1.3%) Paranoia (grade 3, 0.65%) Visual hallucinations (grade 3, 0.65%) Anxiety (grade 3, 0.65%) Sources: https://pubmed.ncbi.nlm.nih.gov/32926604 Page: e5, sup. table 2
4 mg 1 times / day multiple, oral Studied dose Dose: 4 mg, 1 times / day Route: oral Route: multiple Dose: 4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30694697 Page: p.6	unhealthy, CHILD n = 115 Health Status: unhealthy Condition: attention deficit hyperactivity disorder Age Group: CHILD Sex: M+F Food Status: UNKNOWN Population Size: 115 Sources: https://pubmed.ncbi.nlm.nih.gov/30694697 Page: p.6	Disc. AE: Abnormal behavior, Attention deficit hyperactivity disorder... AEs leading to discontinuation/dose reduction: Abnormal behavior (0.9%) Attention deficit hyperactivity disorder (0.9%) Visual hallucinations (0.9%) Visual hallucinations (0.9%) Hypnopompic hallucination (0.9%) Insomnia (3.5%) Hallucinations, mixed (0.9%) Chest pain (0.9%) Irritability (0.9%) Costochondritis (0.9%) Pruritus (0.9%) Sources: https://pubmed.ncbi.nlm.nih.gov/30694697 Page: p.6

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C8 911 CYP3A 214 CYP2C19 1478 CYP2B6 810

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/31674039/	no
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/31674039/	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/31674039/	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/31674039/	no
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/31674039/	weak [Inhibition 0.1 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/31674039/	yes [IC50 0.33 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/31674039/	yes [IC50 1 uM]
CYP3A 298	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/31674039/	yes [IC50 4.7 uM]

PubMed

Title	Date	PubMed
Triple uptake inhibitors: therapeutic potential in depression and beyond.	2007 Sep	17714023
Characterization of the electrophysiological properties of triple reuptake inhibitors on monoaminergic neurons.	2011 Mar	20149268

Patents

Sample Use Guides

In Vivo Use Guide

Adult Attention Deficit Hyperactivity Disorder: Dasotraline 4 mg, 6 mg, 8 mg, flexibly dosed, once daily

Route of Administration: Oral

In Vitro Use Guide

Average in vitro potencies for transporter function inhibition by SEP-225289 have been measured (8, 17, and 10 nM, for the dopamine, norepinephrine, and serotonin transporters, respectively).

Name

Type

Language

DASOTRALINE HYDROCHLORIDE

Official Name

English

1-NAPHTHALENAMINE, 4-(3,4-DICHLOROPHENYL)-1,2,3,4-TETRAHYDRO-, (1R,4S)-, HYDROCHLORIDE

Systematic Name

English

NORSERTRALINE HYDROCHLORIDE, (1R,4S)-TRANS-

Common Name

English

SEP-225289 HYDROCHLORIDE

Code

English

DASOTRALINE HYDROCHLORIDE [USAN]

Common Name

English

Dasotraline hydrochloride [WHO-DD]

Common Name

English

(1R,4S)-4-(3,4-Dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-amine hydrochloride

Systematic Name

English

(1R,4S)-TRANS-NORSERTRALINE HYDROCHLORIDE

Common Name

English

Code System Code Type Description

NCI_THESAURUS

C166517