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Extra resources for Understanding and Managing the Pieces of Major Depressive Disorder

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Indd 49 9/30/2009 12:27:20 PM Major Depressive Disorder Mechanism of Action of Norepinephrine Dopamine Reuptake Inhibitors vs. 2. As their name suggests, norepinephrine dopamine reuptake inhibitors (NDRI) inhibit both the norepinephrine (NET) and the dopamine transporter (DAT), whereas selective norepinephrine inhibitors (NRI) only inhibit NET. This will lead to different actions in different brain regions, depending on the presence of NETs and DATs. indd 50 9/30/2009 12:27:23 PM Chapter 2 Comparing the Regional Effects of Norepinephrine Dopamine Reuptake Inhibitors vs.

Desvenlafaxine has greater NET inhibition than serotonin transporter (SERT) inhibition compared to venlafaxine. Since desvenlafaxine is not a substrate of CYP450 enzymes including 2D6, plasma levels should be more consistent than with venlafaxine. Desvenlafaxine is also unaffected by genetic polymorphisms of CYP450. Thus, the relative amount of NET versus SERT inhibition should also be more consistent, and greater at comparable doses. Desvenlafaxine has been tested for treatment of vasomotor symptoms associated with perimenopause, with positive results.

B) By binding to SERT and thereby inhibiting the reuptake of serotonin, SSRIs allow for more neurotransmitter to remain in the synapse which results in their antidepressant effect. The molecular mechanism of action of SSRIs, including downstream effects on receptors, is illustrated in detail on the following pages. 3. The depressed state is characterized by low serotonin (5HT) levels, upregulated receptors, and a low number of signals in the neuron to release more 5HT. 4. By blocking SERT, selective serotonin reuptake inhibitors (SSRI) cause a rapid increase in 5HT in the somatodendritic area (red circle) with only a little increase in 5HT at the axon (right).

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