1-(3,4-Dichlorophenyl)-3-azabicyclo[3.1.0]hexane

DOV-216,303 (Free Base) is a potent triple serotonin, norepinephrine, and dopamine reuptake inhibitor, with IC50 values of 14 nM, 20 nM and 78 nM for hSERT, hNET and hDAT, respectively[1]. Has antidepressant-like effects and increases monoamine release in the prefrontal cortex of olfactory bulbectomized (OBX) rats[2].

Signaling Pathways >> Neuronal Signaling >> Dopamine Transporter

Research Areas >> Neurological Disease

Signaling Pathways >> Neuronal Signaling >> Serotonin Transporter

IC50: 14 nM (serotonin), 20 nM (norepinephrine), 78 nM (dopamine)[1].

Acute treatment of DOV-216,303 (20 mg/kg, i.p.) significantly increases dopamine, norepinephrine and serotonin levels in both OBX and Sham animals[2]. Chronic treatment with DOV 216,303 (20 mg/kg, i.p., for 17 days) increases extracellular concentrations of dopamine, norepinephrine and serotonin in the medial prefrontal cortex of both OBX and Sham animals and significantly increases extracellular baseline serotonin concentrations[2]. Animal Model: Male Sprague Dawley rats weighing between 290 and 350 g at time of OBX or Sham surgery[2]. Dosage: 20 mg/kg. Administration: I.P. daily for 17days. Result: Increased extracellular concentrations of dopamine, norepinephrine and serotonin in the medial prefrontal cortex of both OBX and Sham animals and significantly increased extracellular baseline serotonin concentrations. Animal Model: Male Sprague Dawley rats weighing between 290 and 350 g at time of OBX or Sham surgery[2]. Dosage: 20 mg/kg. Administration: I.P. once. Result: Significant increases in dopamine, norepinephrine and serotonin levels were measured in both OBX and Sham animals.

[1]. Shao L, et al. Discovery of N-methyl-1-(1-phenylcyclohexyl)methanamine, a novel triple serotonin, norepinephrine, and dopamine reuptake inhibitor. Bioorg Med Chem Lett. 2011 Mar 1;21(5):1438-41.

[2]. Prins J, et al. The putative antidepressant DOV 216,303, a triple reuptake inhibitor, increases monoamine release in the prefrontal cortex of olfactory bulbectomized rats. Eur J Pharmacol. 2010 May 10;633(1-3):55-61.