For the treatment of depression
In 1998, DOV licensed DOV 216,303 from Wyeth-Ayerst. DOV 216,303 is our lead product candidate for the treatment of depression. The product is a triple uptake inhibitor affecting the neurotransmitters norepinephrine, serotonin and dopamine.
These neurotransmitters regulate numerous functions in the central nervous system, and imbalances in them have been linked to a number of psychiatric disorders, including depression. The actions of these neurotransmitters are terminated by specific transport proteins that remove them from synapses in the brain. Antidepressants are thought to produce their therapeutic effects by inhibiting the uptake activity of one or more of these transport proteins, effectively increasing the concentration of these neurotransmitters at their receptors.
In preclinical studies, DOV 216,303 was shown to potently inhibit the uptake of all three neurotransmitters: serotonin, norepinephrine and dopamine. In animal models highly predictive of antidepressant action, DOV 216,303 was more potent than both Tofranil, a dual uptake inhibitor, and Prozac, an SSRI. In one of these models designed to test the onset of activity, DOV 216,303 produced an antidepressant-like action after one week of treatment, as compared to four weeks for Tofranil. Because of its inability to inhibit the uptake of all three neurotransmitters implicated in depression, DOV believes DOV 216,303 may be more effective and have a more rapid onset than other antidepressants.
DOV recently completed a dose-escalating, placebo-controlled, double-blind Phase I clinical trial in France that evaluated the blood levels and side effect profile produced by single doses of DOV 216,303. DOV 216,303 was rapidly absorbed following oral administration, with blood levels proportional to the administered dose. No adverse effects were observed after doses five to ten times higher than the projected therapeutic doses. We initiated a Phase Ib multiple dose-ranging clinical trial of DOV 216,303 in April 2002.
