Brintellix (Vortioxetine) New Antidepressant Approved By FDA Today

[Geaux Tigers!]

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

Vortioxetine is a so-called "serotonin modulator and stimulator".[15] It has been shown to possess the following pharmacological actions:[16][17]

Serotonin transporter (SERT) blocker (i.e. serotonin reuptake inhibitor (SRI)) — Ki (binding affinity) = 1.6 nM
5-HT1A receptor high-efficacy partial agonist/near-full agonist — Ki = 15 nM, IA = 80%
5-HT1B receptor partial agonist — Ki = 33 nM
5-HT3A receptor antagonist — Ki = 3.7 nM
5-HT7 receptor antagonist — Ki = 19 nM
Vortioxetine also has affinity for the β1-adrenergic receptor (Ki = 46 nM), though any actions at this site are unlikely to contribute to its therapeutic effects and likely only to contribute to side effects.[16]

What exactly is a "serotonin modulator and stimulator" and how does this contribute to its antidepressant effects? Based on this, what is the source of its antidepressant efficiency?

 

[sekio]

What exactly is a "serotonin modulator and stimulator"

useless marketing fluff

what is the source of its antidepressant efficiency?

5ht1a full agonism plus SERT blockade I bet

 

[Geaux Tigers!]

It says it's not quite a full agonist at 5ht1a. So, it's like Buspar or Abilify in that regard? Do you think any of its other properties matter?

 

[ebola?]

sounds like its auxiliary activities should ameliorate some of the bullshit that usually comes with SSRIs. . .

ebola

 

[sekio]

It says it's not quite a full agonist at 5ht1a. So, it's like Buspar or Abilify in that regard?

It's much closer to a fullagonist than buspar is (something like 30% max activation)

The 5ht3/7 blockade will also help the side effects profile. ebola is correct.

 

[Dresden]

Yet another piperazine.

 

[ebola?]

Its activity-spectrum seems friendlier than other piperazines though.

ebola

 

[endotropic]

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

Vortioxetine is a so-called "serotonin modulator and stimulator".[15] It has been shown to possess the following pharmacological actions:[16][17]

Serotonin transporter (SERT) blocker (i.e. serotonin reuptake inhibitor (SRI)) — Ki (binding affinity) = 1.6 nM
5-HT1A receptor high-efficacy partial agonist/near-full agonist — Ki = 15 nM, IA = 80%
5-HT1B receptor partial agonist — Ki = 33 nM
5-HT3A receptor antagonist — Ki = 3.7 nM
5-HT7 receptor antagonist — Ki = 19 nM
Vortioxetine also has affinity for the β1-adrenergic receptor (Ki = 46 nM), though any actions at this site are unlikely to contribute to its therapeutic effects and likely only to contribute to side effects.[16]

What exactly is a "serotonin modulator and stimulator" and how does this contribute to its antidepressant effects? Based on this, what is the source of its antidepressant efficiency?

I was surprised to see for common side effects, "nausea, vomiting, diarrhea" considering the 5-HT3 antagonist activity. 5-HT3 antagonists are used therapeutically to prevent those exact symtoms.

 

[dingophone]

It should be noted that 5HT-7 blockade is shown to contribute to antidepressant effects. What activity does it have at B1? Also, seems like an antidepressant that wouldn't interfere too too much with psychedelics

 

[ebola?]

Also, seems like an antidepressant that wouldn't interfere too too much with psychedelics.

Honestly, I've tripped fine the day after having taken mirtazapine at night for sleep, but this was at 7.5 to 15 mg. So Brintellix...well, its high affinity for 5ht1a might preclude psychedelics' activity there, though Brintellix itself might provide enough suitable activity, given its high efficacy. It doesn't antagonize 5ht2a, but it does inhibit SERT, so we'd still expect to see the same downregulation of 5ht2a receptors that we see with SSRIs, which can cause mild to moderate attenuation of psychedelics' effects.

ebola

 

[dingophone]

Honestly, I've tripped fine the day after having taken mirtazapine at night for sleep, but this was at 7.5 to 15 mg. So Brintellix...well, its high affinity for 5ht1a might preclude psychedelics' activity there, though Brintellix itself might provide enough suitable activity, given its high efficacy. It doesn't antagonize 5ht2a, but it does inhibit SERT, so we'd still expect to see the same downregulation of 5ht2a receptors that we see with SSRIs, which can cause mild to moderate attenuation of psychedelics' effects.

ebola

Aren't TCAs known to potentiate rather than cut down on trips? I've always read that anyway. But with the SERT affinity you do raise an interesting point. For many it would seem that this mechanism of action is responsible for cutting down on trips significantly. I recall reading somewhere, though, that a number of SSRIs (I believe fluoxetine, fluvoxamine, and MAYBE sertraline) were actually found to bind to 5HT2A as antagonists or weak partial agonists. It's entirely possible that I could be completely fucking wrong there though

It's also interesting to note that my first couple of trips occurred while I was taking venlafaxine and they were quite... active. Since then, I've gotten off the drug (which was an awful experience!) and I've not seen too much change in my psychedelic experiences. I've read elsewhere that venlafaxine has little effect on psychedelics as well. Coincidentally, venlafaxine has been shown to have no significant (>100000nM) affinity for the 5ht2a receptor.

One other note; a lot of the SRRIs also have strong sigma1 agonist properties. This effect is also notably absent in venlafaxine and TCAs. Perhaps this might have something to do with it somewhere along the path? AFAIK sigma pathways are still not well understood.

 

[ebola?]

Aren't TCAs known to potentiate rather than cut down on trips?

I've seen this on erowid and heard it anecdotally, but can anyone substantiate this with something more definitive?

ebola

 

[tweex]

It should be noted that 5HT-7 blockade is shown to contribute to antidepressant effects.

I'm not sure how much this plays out in reality. Lurasidone is a very potent 5-HT7 antagonist, and IME not much of an antidepressant, but a bit thermogenic for this reason.

 

[dingophone]

I'm not sure how much this plays out in reality. Lurasidone is a very potent 5-HT7 antagonist, and IME not much of an antidepressant, but a bit thermogenic for this reason.

For some people it seems to be a pretty decent AD. You make a good point though, not everyone functions the exact same way. The nervous system is quite complicated

I also found a somewhat non-answer to my 5HT2a functional selectivity question! Serotonin activates both the A2 and C pathways, but because it does not do so selectively, there is not much (less?) of a "psychedelic" effect. However a few studies show that serotonin can activate A2 preferentially, so it's still a bit confusing to me. Another interesting proposition is that DMT could be involved in A2 cascade.

 

[Doldrugs]

I just started this drug. Is there any danger in combining it with psychedelics like acid, shrooms, or mescaline? Has anyone tried taking psychedelics on it ?