dasotraline   Click here for help

GtoPdb Ligand ID: 8308

Synonyms: (1R,4S)-trans-norsertraline | SEP-225,289 | SEP-225289
Compound class: Synthetic organic
Comment: Dasotraline is a triple reuptake inhibitor [1,3]. Such compounds are also known as serotonin-norepinephrine-dopamine reuptake inhibitors, or SNDRIs. Structurally, dasotraline is a stereoisomer of an active metabolite of sertraline, a selective serotonin reuptake inhibitor (SSRI) antidepressant.
2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 1
Hydrogen bond donors 1
Rotatable bonds 1
Topological polar surface area 26.02
Molecular weight 291.06
XLogP 4.75
No. Lipinski's rules broken 0
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Canonical SMILES NC1CCC(c2c1cccc2)c1ccc(c(c1)Cl)Cl
Isomeric SMILES N[C@@H]1CC[C@H](c2c1cccc2)c1ccc(c(c1)Cl)Cl
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
Bioactivity Comments
To date, IC50 values for the inhibition of monoamine transporters by dasotraline has only been reported in a meeting abstract (Schreiber R, Lew R, Hardy L, Cremers T, et al (2009) Pharmacological characterization of the triple monoamine transporter inhibitor SEP-225289. Society for Neuroscience (Abstract no. 549.8/X2)). IC50s for inhibiton of rat SERT, NET and DAT are 11, 6 and 4nM respectively.
In vivo drug occupancy has been evaluated as a more accurate indication of a drug's transporter binding profile. PET results show that dasotraline ocupies ~85% of dopamine transporter sites, whereas serotonin transporter occupancy was too low to calculate accurately [2]. This result is despite in vitro binding to each transporter being similar.