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Re: Vilazodone vs Nefazodone - 5-HT receptors

Posted by linkadge on November 14, 2010, at 20:12:24

In reply to Re: Vilazodone vs Nefazodone - 5-HT receptors, posted by morgan miller on November 14, 2010, at 19:34:48

>Sorry, I guess I didn't make myself clear. Since >SSRIs obviously have a significant impact on >increasing the amount of serotonin in the brain,

Necessarily not true. When given acutely maybe, but there are conflicting reports as to whether chronic administration of SSRIs actually increases serotonin neurotransmission. There are many compensatory changes that occur when SSRRIs are administered chronicaly.

According to wikipedia: "Certain SSRI medications have been shown to lower serotonin levels below the baseline after chronic use, despite initial increases in serotonin"

http://en.wikipedia.org/wiki/Serotonin

See the previous study I had posted above on citalopram:

"Citalopram administration caused a suppression of 5-HT synthesis at all time points. CIT treatment also caused a reduction in forebrain 5-HIAA content. Following chronic CIT treatment, forebrain 5-HT stores were more sensitive to the depleting effects of acute decarboxylase inhibition."

Also, the equlivlant or superior efficacy of tianeptine in anxious depression seems to argue against the low serotonin theory.

>and don't have any other action that could >explain their antidepressant effects,

B.S.

There are many other nonserotonergic targets of the SSRIs. Certain SSRIs like escitalopram have direct effects on adenylyl cyclase. SSRIs have been shown to exhibit anti-inflamatory and immune modulating effects independant of the serotonin reuptake inhibition. In addition other targets of the SSRIs include sigma receptors (sertraline, fluvoxamine), ion channels (calcium, sodium, potasium: trek-1) and monoamine receptors (fluoxetine), nitric oxide synthase and acetylcholine (paroxetine). In addition all of the SSRIs have been shown to dramatically increase the activity of the potent gabaergic neurosteroid allopregnanalone, a metabolite of progesterone which is low in depression. Interstingly remeron also increases the synthesis of allopregnanalone but it has no effect on the serotonin transporter. Some of the SSRIs have effects on ERK kinases, protein kinases as well as NMDA receptor function.

The SSRI antidepresants have this effect, but not any random agents with SERT binding. Many of these targets have shown antidepressant effects in animal models.


Linkadge


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