This topic contains 2 replies, has 2 voices, and was last updated by Pereise1 4 months, 2 weeks ago. This post has been viewed 266 times
- October 17, 2018 at 2:48 pm #8088
Hello all, I found an interesting study while I was researching the mechanism of action of Vortioxetine that may be of interest to those taking SSRIs, and for PWN as a whole:
Differentiated effects of the multimodal antidepressant vortioxetine on sleep architecture: Part 2, pharmacological interactions in rodents suggest a role of serotonin-3 receptor antagonism.
Leiser SC1, Iglesias-Bregna D2, Westrich L2, Pehrson AL2, Sanchez C2.
Antidepressants often disrupt sleep. Vortioxetine, a multimodal antidepressant acting through serotonin (5-HT) transporter (SERT) inhibition, 5-HT3, 5-HT7 and 5-HT1D receptor antagonism, 5-HT1B receptor partial agonism, and 5-HT1A receptor agonism, had fewer incidences of sleep-related adverse events reported in depressed patients. In the accompanying paper a polysomnographic electroencephalography (sleep-EEG) study of vortioxetine and paroxetine in healthy subjects indicated that at low/intermediate levels of SERT occupancy, vortioxetine affected rapid eye movement (REM) sleep differently than paroxetine. Here we investigated clinically meaningful doses (80-90% SERT occupancy) of vortioxetine and paroxetine on sleep-EEG in rats to further elucidate the serotoninergic receptor mechanisms mediating this difference. Cortical EEG, electromyography (EMG), and locomotion were recorded telemetrically for 10 days, following an acute dose, from rats receiving vortioxetine-infused chow or paroxetine-infused water and respective controls. Sleep stages were manually scored into active wake, quiet wake, and non-REM or REM sleep. Acute paroxetine or vortioxetine delayed REM onset latency (ROL) and decreased REM episodes. After repeated administration, vortioxetine yielded normal sleep-wake rhythms while paroxetine continued to suppress REM. Paroxetine, unlike vortioxetine, increased transitions from non-REM to wake, suggesting fragmented sleep. Next, we investigated the role of 5-HT3 receptors in eliciting these differences. The 5-HT3 receptor antagonist ondansetron significantly reduced paroxetine’s acute effects on ROL, while the 5-HT3 receptor agonist SR57227A significantly increased vortioxetine’s acute effect on ROL. Overall, our data are consistent with the clinical findings that vortioxetine impacts REM sleep differently than paroxetine, and suggests a role for 5-HT3 receptor antagonism in mitigating these differences.
So basically, the serotonin 5-HT3 receptor is involved in sleep. It’s commonly known as the nausea receptor, but also has a role in the wakefulness effects of (ar)modafinil. (Ar)modafinil stimulates the 5-HT3 receptor in parts of the brain that where it increases wakefulness, although sometimes also in the Chemoreceptor Trigger Zone (CTZ), where this receptor strongly promotes nausea and vomiting. So it makes sense that a simple SSRI like paroxetine, which increases all serotonin receptor agonism including 5-HT3, would reduce REM but also disrupt sleep. Vortioxetine, on the other hand, is also a 5-HT3 antagonist and doesn’t change sleep parameters too much.
So the gist of this is, perhaps it would be useful for PWN to take a 5-HT3 antagonist before sleep? Research suggests that it can increase slow wave sleep (Reference) and can also improve sleep disordered breathing (Reference).October 22, 2018 at 11:15 pm #8124
Hello, @pereise1 – thanks for sharing this info! I have been reading as much as I can & looked up the Med list on this site, and it doesn’t list either of the 2 SSRIs you mentioned (paroxetine or Vortioxetine.) I’m trying to compile lists of the different meds & what they are supposed to do (what symptoms and/or underlying issues they’re used for in regard to PWN) so I can have a better idea of what I might want to try when I talk to my Neuro. Would either of the 2 you posted about go under/with Fluxetine (Prozac) or Sertaline (Zoloft)?November 7, 2018 at 12:58 pm #8224
Hello, @pereise1 – thanks for sharing this info! I have been reading as much as I can & looked up the Med list on this site, and it doesn’t list either of the 2 SSRIs you mentioned (paroxetine or Vortioxetine.) I’m trying to compile lists of the different meds & what they are supposed to do (what symptoms and/or underlying issues they’re used for in regard to PWN) so I can have a better idea of what I might want to try when I talk to my Neuro. Would either of the 2 you posted about go under/with Fluxetine (Prozac) or Sertaline (Zoloft)?
Sorry for the late reply, but yeah, they’re all SSRIs. As for the receptors that they all bind to significantly:
Paroxetine: SERT (0.34nm)
Sertaline: SERT (0.4nm), Neurosteroidogenesis agonist
Fluoxetine: SERT (1nm), 5-HT2C antagonist (72nm), Maybe Sigma-1 agonist, Neurosteroidogenesis agonist
Vortioxetine: SERT (1.6nm), NET (113nm), 5-HT1A agonist (15nm), 5-HT2B partial agonist (33nm), 5-HT3 antagonist (3.7nm)
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