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Therapeutic Area: Major Depression
Phase of Development: Phase II

Development Status:
Phase II, Extended Release prototypes are in development.

Production Description
Over the past 25 years, progress in the treatment of major depression has been limited to an improvement in the side effect profile. The serotonin reuptake inhibitors, while safer than imipramine and other tricyclics, are less efficacious.

Forty percent or more of major depression patients do not respond to currently available antidepressants. There is a need for an antidepressant with stronger activity that could treat a larger selection of depressed patients.

FKB01MD is a strong antidepressant that down regulates 5HT2 receptors in animals overnight. FKB01MD has 5 mechanisms of action including 5HT reuptake blockade, 5HT2 agonism, 5HT1A agonism, and actions on the 5HT1D central receptors.

FKB01MD is active in the usual animal models of depression especially in the ability to inhibit muricidal behavior (i.e. mouse killing) in rats where it is more active than fluoxetine or desipramine. It was also more active than SSRIs in the Porsolt test.

The robust efficacy demonstrated by FKB01MD in animal models that predict antidepressant potential in man is believed to reflect this drug’s multiple interactions with serotonergic mechanisms. This multiplicity of action consists of the incorporation of several distinct serotonergic mechanisms found in other clinically effective antidepressants into a single molecule, FKB01MD. This agent exhibits the 5HT reuptake blockade found in tricyclic antidepressants, 5HT2 receptor blockade found in trazodone, and 5HT1A interactions found in azapirones. Additionally, FKB01MD exhibits a unique agonist interaction with the central terminal 5HT1D autoreceptor. It is anticipated that the interactions of FKB01MD with multiple subtypes of 5HT2 receptors will produce earlier and greater adaptation of serotonergic systems than other antidepressants, and this will in turn result in a more rapid onset and greater degree of antidepressant efficacy.

Clinical Trials
Phase I studies indicate no areas of concern. Pharmacokinetic studies indicate the absolute bioavailability is approximately 17% and the half-life is approximately 4 hours. Adverse events were mild and mostly limited to lightheadedness and nausea. Several short term Phase II efficacy studies have been performed. Doses of 10-30 mg BID were well tolerated by depressed patients. In certain patients in the Phase II studies the drug showed strong antidepressant activity.

Developmental and licensing opportunities are available.