Dasotraline is a triple reuptake inhibitor that blocksdopamine,norepinephrine, andserotonintransporters withIC₅₀values of 4, 6, and 11 nM, respectively.

IC50: 4 nM (dopamine transporter), 6 nM (norepinephrine transporter),11 nM (5-HT transporter)^[1]

The present in-vivoelectrophysiological study is undertaken to determine the effects of the triple reuptake inhibitor Dasotraline (SEP-225289) on the neuronal activities of locus coeruleus (LC) NE, ventral tegmental area (VTA) DA and dorsal raphe (DR) 5-HT neurons. Administered acutely, Dasotraline dose-dependently decreases the spontaneous firing rate of LC NE, VTA DA and DR 5-HT neurons through the activation of α₂, D₂and 5-HT_1Aautoreceptors, respectively. Dasotraline predominantly inhibits the firing rate of LC NE neurons while producing only a partial decrease in VTA DA and DR 5-HT neuronal discharge. Dasotraline is equipotent at inhibiting 5-HT and NE transporters since it prolongs to the same extent the time required for a 50% recovery (RT₅₀) of the firing activity of dorsal hippocampus CA3 pyramidal neurons from the inhibition induced by microiontophoretic application of 5-HT and NE. The recovery time (RT), from the suppression of hippocampus pyramidal neuron firing activity following microiontophoresis application of 5-HT and NE, is assessed by determining the RT₅₀values before and after the acute intravenous administration of cumulative doses of Dasotraline (1–8 mg/kg). Although Dasotraline (1 and 2 mg/kg) does not modify the firing activity of CA3 pyramidal neurons, a significant reduction (~50%) is detected with the highest dose (8 mg/kg). In rats pre-treated with WAY100635, Dasotraline (0.5-2 mg/kg i.v.) elicits a significant increase in DR 5-HT firing rate. In rats pre-treated with WAY100635, Dasotralinesignificantly increases the number of single spikes and bursts^[1].

292.20

C₁₆H₁₅Cl₂N

675126-05-3

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

DMSO : ≥ 31 mg/mL(106.09 mM)

*"≥" means soluble, but saturation unknown.