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Serotonin'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.


"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."


Humans punish themselves endlessly
for not being what they believe they should be.
-Don Miguel Ruiz-




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