Psycho-Babble Medication Thread 1118082

Shown: posts 1 to 19 of 19. This is the beginning of the thread.

 

Serotonin 5HT3...it's that gut feeling..MAJORLY...

Posted by Jay2112 on January 9, 2022, at 17:24:48

I have had SEVERE episodes of vomiting and stomach distress (sorry for the graphic) over the past 5 or so years, when my illness was at it's worse (touch wood). So, like always, after getting a clean bill of health from a stomach scope procedure, I researched the *&^% out of stomach problems. Mainly, it seemed I have a 'nervous' stomach...and I was also on too high a dose of Effexor and Lithium. (both strong serotonergic drugs.) And...that 5HT3 receptor was a b*tch! 5HT3 agonism is also a part of vagus nerve stimulation..and why in the world would anybody WANT this?? (VNS)

Now, reading further, it seems that 5HT3 antagonists have a strong antidepressant effect. But, insurance companies seem to limit the use of 5HT3 antagonist drugs for chemotherapy. (with all due respect) But...damn...these in combo with an SRI might be a real breakthrough. Yeah, I know Remeron has 5H3 antagonist properties...but still! AS WELL, there is glutamatergic stimulation, which I imagine leads to downregulation. Anyone know what antipsychotics have the strongest 5HT3 antagonist properties? Vortioxetine seems to be the only other (available in Canada) antidepressant that does, and I MAY try this next.

from: https://pharmrev.aspetjournals.org/content/71/3/383#sec-23

"Vortioxetine provides further evidence for the engagement of 5-HT3R ligands in the modulation of neurotransmitter release and antidepressant activity. This multimodal agent combines the SSRI mode of action (i.e., inhibition of the serotonin transporter) with 5-HT3R antagonism to augment 5-HT availability in synapses (Stahl, 2015). The latter most likely contributes to vortioxetines clinical antidepressant effects (Pehrson and Sanchez, 2014; Sanchez et al., 2015). The blockade of 5-HT3R by vortioxetine disinhibits pyramidal neurons through elimination of GABAergic inhibition. The resultant increase in glutamatergic transmission stimulates serotonergic neurons in the raphe nucleus to release 5-HT (Stahl, 2015). Similarly, ondansetron demonstrates synergistic antidepressant-like effects in the FST when used as an adjunct to SSRIs (Redrobe and Bourin, 1997; Bétry et al., 2015). The effect is most likely due to the enhancement of SSRI action on extracellular 5-HT through 5-HT3R blockade."

Jay

 

Re: Serotonin 5HT3...it's that gut feeling..MAJORLY...

Posted by undopaminergic on January 10, 2022, at 12:29:06

In reply to Serotonin 5HT3...it's that gut feeling..MAJORLY..., posted by Jay2112 on January 9, 2022, at 17:24:48

For some reason, however, nausea appears to be the most common adverse effect of vortioxetine, but ondansetron often works to counteract it.

-undopaminergic

 

Re: Serotonin 5HT3...it's that gut feeling..MAJORLY... » undopaminergic

Posted by Jay2112 on January 10, 2022, at 20:44:15

In reply to Re: Serotonin 5HT3...it's that gut feeling..MAJORLY..., posted by undopaminergic on January 10, 2022, at 12:29:06

> For some reason, however, nausea appears to be the most common adverse effect of vortioxetine, but ondansetron often works to counteract it.
>
> -undopaminergic
>

It really seems there are paradoxes at work in so many psych drugs. Could it be some of the antagonism loops back, making the receptors more, well, receptive to existing 5HT? I am not sure of the terminology....

I am just thinking in the oppposite example of say Lithium agonizing glutamine receptors, and actually downregulating their sensitivity??

Jay

 

Re: Serotonin 5HT3...it's that gut feeling..MAJORLY... » Jay2112

Posted by linkadge on January 11, 2022, at 6:44:12

In reply to Re: Serotonin 5HT3...it's that gut feeling..MAJORLY... » undopaminergic, posted by Jay2112 on January 10, 2022, at 20:44:15

>Could it be some of the antagonism loops back, >making the receptors more, well, receptive to >existing 5HT? I am not sure of the terminology....

It could be that the effect of serotonin reuptake exceeds the 5-ht3 blockade.

Interestingly, it was recently discovered that bupropion has some ability to block 5-ht3.

Linkadge

 

Re: Serotonin 5HT3...it's that gut feeling..MAJORLY...

Posted by SLS on January 11, 2022, at 10:56:28

In reply to Re: Serotonin 5HT3...it's that gut feeling..MAJORLY... » Jay2112, posted by linkadge on January 11, 2022, at 6:44:12

Hi.

Perhaps binding affinity would be necessary to factor in to help determine the net effect of compounds competing for the same receptor.

I think this is where empirical studies investigating in vivo results of biological manipulations become valuable.


- Scott

 

Re: Serotonin 5HT3...it's that gut feeling..MAJORLY...

Posted by undopaminergic on January 11, 2022, at 12:33:28

In reply to Re: Serotonin 5HT3...it's that gut feeling..MAJORLY... » Jay2112, posted by linkadge on January 11, 2022, at 6:44:12

> >Could it be some of the antagonism loops back, >making the receptors more, well, receptive to >existing 5HT? I am not sure of the terminology....
>
> It could be that the effect of serotonin reuptake exceeds the 5-ht3 blockade.

In that case, however, you would expect SSRIs to be even worse associated with nausea than vortioxetine, which also has milder sexual side effects.

-undopaminergic

 

Re: Serotonin 5HT3...it's that gut feeling..MAJORLY...

Posted by linkadge on January 13, 2022, at 19:08:09

In reply to Re: Serotonin 5HT3...it's that gut feeling..MAJORLY..., posted by undopaminergic on January 11, 2022, at 12:33:28

Does vortioxetine produce more nausea than SSRIs? I had some nasty initial nausea with sertraline and paroxetine, but I have never taken vortioxetine.

Linkadge

 

Re: Serotonin 5HT3...it's that gut feeling..MAJORLY...

Posted by linkadge on January 13, 2022, at 19:10:06

In reply to Re: Serotonin 5HT3...it's that gut feeling..MAJORLY..., posted by undopaminergic on January 11, 2022, at 12:33:28

According to the comparison table on wikipedia, nausea was more common with duloxetine than vortioxetine.

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

Linkadge

 

Re: Serotonin 5HT3...it's that gut feeling..MAJORLY...

Posted by linkadge on January 13, 2022, at 19:22:47

In reply to Re: Serotonin 5HT3...it's that gut feeling..MAJORLY..., posted by undopaminergic on January 11, 2022, at 12:33:28

To complicate matters, there are at least 5 subtypes of the 5-ht3 receptor (5-ht3a, 5-ht3b, 5-ht3c, 5-ht3d, 5-ht3e). From what I understand, vortioxetine shows preference for 5-ht3a which are expressed more the CNS (hence it may not block 5-ht3 in the gut). Reading more ...

Linkadge

 

Re: Serotonin 5HT3...it's that gut feeling..MAJORLY...

Posted by undopaminergic on January 14, 2022, at 10:51:27

In reply to Re: Serotonin 5HT3...it's that gut feeling..MAJORLY..., posted by linkadge on January 13, 2022, at 19:08:09

> Does vortioxetine produce more nausea than SSRIs?

Yes. It seems to be the absolute most common adverse effect -- or even *effect* in general. This conclusion is based on the reviews on drugs.com. If you persevere, it often goes away with time.

However, according to Wikipedia, nausea is even more common with duloxetine:
https://en.wikipedia.org/wiki/Vortioxetine
So I'm not sure.

-undopaminergic

 

Re: Serotonin 5HT3...it's that gut feeling..MAJORLY...

Posted by undopaminergic on January 14, 2022, at 10:57:53

In reply to Re: Serotonin 5HT3...it's that gut feeling..MAJORLY..., posted by linkadge on January 13, 2022, at 19:22:47

> To complicate matters, there are at least 5 subtypes of the 5-ht3 receptor (5-ht3a, 5-ht3b, 5-ht3c, 5-ht3d, 5-ht3e). From what I understand, vortioxetine shows preference for 5-ht3a which are expressed more the CNS (hence it may not block 5-ht3 in the gut). Reading more ...
>
> Linkadge

Memantine is a 5-HT3 antagonist too. Any others?

-undopaminergic

 

Re: Serotonin 5HT3...it's that gut feeling..MAJORLY... » undopaminergic

Posted by Jay2112 on January 16, 2022, at 17:48:24

In reply to Re: Serotonin 5HT3...it's that gut feeling..MAJORLY..., posted by undopaminergic on January 14, 2022, at 10:57:53

> > To complicate matters, there are at least 5 subtypes of the 5-ht3 receptor (5-ht3a, 5-ht3b, 5-ht3c, 5-ht3d, 5-ht3e). From what I understand, vortioxetine shows preference for 5-ht3a which are expressed more the CNS (hence it may not block 5-ht3 in the gut). Reading more ...
> >
> > Linkadge
>
> Memantine is a 5-HT3 antagonist too. Any others?
>
> -undopaminergic
>

I did mention Remeron/mirtazapine. This stuff works AMAZING for stomach/nausea problems! I wonder what mirtazapine and vortioxetine would do together?

UD, are you still on the vortioxetine? How is it going so far?

Jay

 

Re: Serotonin 5HT3...it's that gut feeling..MAJORLY... » Jay2112

Posted by undopaminergic on January 17, 2022, at 7:31:05

In reply to Re: Serotonin 5HT3...it's that gut feeling..MAJORLY... » undopaminergic, posted by Jay2112 on January 16, 2022, at 17:48:24

>
> UD, are you still on the vortioxetine? How is it going so far?
>

I'm not on vortioxetine *yet*, but I hope soon.

-undopaminergic

 

Re: Serotonin 5HT3...it's that gut feeling..MAJORLY...

Posted by Lamdage22 on January 19, 2022, at 8:07:46

In reply to Re: Serotonin 5HT3...it's that gut feeling..MAJORLY... » Jay2112, posted by undopaminergic on January 17, 2022, at 7:31:05

Good luck!

 

Re: Serotonin 5HT3...it's that gut feeling..MAJORLY...

Posted by undopaminergic on January 19, 2022, at 8:19:54

In reply to Re: Serotonin 5HT3...it's that gut feeling..MAJORLY..., posted by Lamdage22 on January 19, 2022, at 8:07:46

> Good luck!

Thanks.

-undopaminergic

 

Re: Serotonin 5HT3...it's that gut feeling..MAJORLY...

Posted by Lamdage22 on January 19, 2022, at 12:24:16

In reply to Re: Serotonin 5HT3...it's that gut feeling..MAJORLY..., posted by undopaminergic on January 19, 2022, at 8:19:54

Maybe youll get well enough to pursue psychodynamic work again.

 

Re: Serotonin 5HT3...it's that gut feeling..MAJORLY...

Posted by undopaminergic on January 19, 2022, at 13:20:42

In reply to Re: Serotonin 5HT3...it's that gut feeling..MAJORLY..., posted by Lamdage22 on January 19, 2022, at 12:24:16

> Maybe youll get well enough to pursue psychodynamic work again.

Even if it were to relieve the main complaint, the apathy, it would not readily give me access to a (skilled) psychodynamic therapist. Although it would certainly help my ability to do free association on my own.

-undopaminergic

 

Re: Serotonin 5HT3...it's that gut feeling..MAJORLY...

Posted by Lamdage22 on January 20, 2022, at 0:03:58

In reply to Re: Serotonin 5HT3...it's that gut feeling..MAJORLY..., posted by undopaminergic on January 19, 2022, at 13:20:42

That is what I meant. I cant fathom how you do it but if it worked in the past

 

Re: Serotonin 5HT3...it's that gut feeling..MAJORLY...

Posted by undopaminergic on January 20, 2022, at 8:25:02

In reply to Re: Serotonin 5HT3...it's that gut feeling..MAJORLY..., posted by Lamdage22 on January 20, 2022, at 0:03:58

> That is what I meant. I cant fathom how you do it but if it worked in the past

It worked powerfully only once. Maybe a little on some other occasions.

The one time it really worked, I was trying to write an essay about truth and delusion. I was getting quite involved in it.

-undopaminergic


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