Dasotraline

Dasotraline (INN;[1] former developmental code name SEP-225,289) is a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI) that was under development by Sunovion for the treatment of attention-deficit hyperactivity disorder (ADHD) and binge eating disorder (BED).[2][3][4][5] Structurally, dasotraline is a stereoisomer of desmethylsertraline (DMS), which is an active metabolite of the marketed selective serotonin reuptake inhibitor (SSRI) antidepressant sertraline (Zoloft).

Dasotraline
Identifiers
IUPAC name
  • (1R,4S)-4-(3,4-Dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthalenamine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC16H15Cl2N
Molar mass292.20 g·mol−1
3D model (JSmol)
SMILES
  • C1C[C@H](C2=CC=CC=C2[C@@H]1C3=CC(=C(C=C3)Cl)Cl)N
InChI
  • InChI=1S/C16H15Cl2N/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/t11-,16+/m0/s1
  • Key:SRPXSILJHWNFMK-MEDUHNTESA-N
 NY (what is this?)  (verify)

Adverse Effects

In phase I clinical trials for ADHD, test subjects reported the following side effects:[6]

History

In 2017, the U.S. Food and Drug Administration accepted Sunovion's New Drug Application (NDA) for review for the treatment of ADHD;[7] however, the NDA was ultimately rejected citing the need for additional studies to determine efficacy and tolerability.[8][9][10] In July 2019, Sunovion’s NDA for the treatment of BED was accepted with an expected action date of May 2020.[11] In May 2020, Sunovion halted its drug development program for dasotraline, withdrawing both NDAs for ADHD and BED.[12]

See also

References
  1. "International Nonproprietary Names for Pharmaceutical Substances (INN)" (PDF). WHO Drug Information. WHO. 27 (4). 2013. Retrieved 4 November 2014.
  2. Chen Z, Skolnick P (September 2007). "Triple uptake inhibitors: therapeutic potential in depression and beyond". Expert Opinion on Investigational Drugs. 16 (9): 1365–77. doi:10.1517/13543784.16.9.1365. PMID 17714023. S2CID 20271918.
  3. DeLorenzo C, Lichenstein S, Schaefer K, Dunn J, Marshall R, Organisak L, et al. (July 2011). "SEP-225289 serotonin and dopamine transporter occupancy: a PET study". Journal of Nuclear Medicine. 52 (7): 1150–5. doi:10.2967/jnumed.110.084525. PMC 3856248. PMID 21680689.
  4. Ziegler L, Küffer G, Euler E, Wilhelm K (August 1990). "[Arthrographic imaging of ganglions of the hand]" [Arthrographic imaging of ganglions of the hand]. RöFo (in German). 153 (2): 143–6. doi:10.1055/s-2008-1033352. PMID 2168068.
  5. Guiard B, Chenu F, El Mansari M, Blier P (2009). "P.1.c.059 Electrophysiological properties of the triple reuptake inhibitor SEP 225289 on monoaminergic neurons". European Neuropsychopharmacology. 19: S285. doi:10.1016/S0924-977X(09)70419-5. S2CID 54263757.
  6. Koblan KS, Hopkins SC, Sarma K, Jin F, Goldman R, Kollins SH, Loebel A (November 2015). "Dasotraline for the Treatment of Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Trial in Adults". Neuropsychopharmacology. 40 (12): 2745–52. doi:10.1038/npp.2015.124. PMC 4864650. PMID 25948101.
  7. "Sunovion Announces FDA Acceptance for Review of New Drug Application for Dasotraline for the Treatment of ADHD" (Press release). Marlborough, Massachusetts: Sunovion. Business Wire. November 10, 2017. Retrieved 2018-05-01.
  8. "FDA Issues a Complete Response Letter for New Drug Application for Dasotraline for the Treatment of Adhd". Sumitomo Dainippon Pharma Co., Ltd. August 31, 2018.
  9. "Pipeline Report: Brand Drugs" (PDF). Welldyne. February 2018. pp. 1, 4. Retrieved 1 May 2018.
  10. Clinical trial number NCT02276209 for "Dasotraline Adult ADHD Study" at ClinicalTrials.gov
  11. "Sunovion Announces Acceptance by the US FDA of the New Drug Application for Dasotraline for the Treatment of Adults with Moderate-to-Severe Binge Eating Disorder". Sumitomo Dainippon Pharma Co., Ltd. July 30, 2019.
  12. "Sunovion Discontinues Dasotraline Program". www.businesswire.com. 13 May 2020. Retrieved 27 June 2020.

Further reading
Liming Shao Patent
  • US application 2007203111, Shao L, Wang F, Malcolm SC, Hewitt MC, Bush LR, Ma J, Varney MA, Campbell U, Engel SR, Hardy LW, Koch P, Campbell JE, "Cycloalkylamines as monoamine reuptake inhibitors", published 2007-08-30, assigned to Sepracor Inc.
Asymmetry Patent
  • US patent 7129378, Han X, Krishnamurthy D, Senanayake CH, Lu Z-H, "Method of preparing amine stereoisomers", published 2005-07-28, assigned to Apsinterm LLC
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