4 ms·

It would probably be any SSRI though?

PragmaticPulp 6y ago
No, it's strictly Fluvoxamine as far as we know. SSRIs aren't all interchangeable, especially when it comes to side effects. Fluvoxamine is very different than other SSRIs because it has significant effects at the sigma-1 receptor. The only other SSRI with significant sigma-1 activity is Sertraline, but it has the opposite effect at sigma-1. However, it's possible that the anti-COVID properties are unrelated to Fluvoxamine's actions at the serotonin transporter or the sigma-1 receptor. We just don't know.
- mrandish 6y ago
  The similarly named Fluoxetine has lesser (but still significant) effects at Sigma-1. Since Fluoxetine is so widely distributed (because it's Prozac), there is quite a bit of observational data that Fluoxetine is also correlated with reduced clinical severity. Obviously, even a strong correlation is not causation but it is certainly grounds for prioritizing investigation, especially since Fluoxetine/Prozac is very well-tolerated, inexpensive and widely available in mass quantity.
  - PragmaticPulp 6y ago
    Fluvoxamine has the highest sigma-1 affinity by far. Fluoxetine's affinity is about an order of magnitude lower. We don't even know if sigma-1 is responsible for the effects observed, but it wouldn't make sense to give someone Fluoxetine instead of Fluvoxamine (which is also widely available), especially when it would require overdose levels of Fluoxetine to achieve similar sigma-1 effects. More numbers available in the full text here: https://pubmed.ncbi.nlm.nih.gov/24508523/ https://pubmed.ncbi.nlm.nih.gov/24508523/
WalterSear 6y ago
It's suspected to be a specific side effect, not a part of the reuptake inhibition.
xkcd-sucks 6y ago
Generally speaking, "SSRI" is an ideal goal which isn't perfectly realized; all drugs in that class bind "off-target" to proteins other than SERT. In this case, fluvoxamine pharmacology is pretty clean and there is experimental evidence only for binding to sigma-1 receptor in addition to SERT (also to a whole bunch of CYP enzymes). Unfortunately the function of sigma-1 is not well understood but it affects calcium signalling in intracellular compartments where covid-19 replicates

No, it's strictly Fluvoxamine as far as we know. SSRIs aren't all interchangeable, especially when it comes to side effects. Fluvoxamine is very different than other SSRIs because it has significant effects at the sigma-1 receptor. The only other SSRI with significant sigma-1 activity is Sertraline, but it has the opposite effect at sigma-1. However, it's possible that the anti-COVID properties are unrelated to Fluvoxamine's actions at the serotonin transporter or the sigma-1 receptor. We just don't know.

mrandish 6y ago
The similarly named Fluoxetine has lesser (but still significant) effects at Sigma-1. Since Fluoxetine is so widely distributed (because it's Prozac), there is quite a bit of observational data that Fluoxetine is also correlated with reduced clinical severity. Obviously, even a strong correlation is not causation but it is certainly grounds for prioritizing investigation, especially since Fluoxetine/Prozac is very well-tolerated, inexpensive and widely available in mass quantity.
- PragmaticPulp 6y ago
  Fluvoxamine has the highest sigma-1 affinity by far. Fluoxetine's affinity is about an order of magnitude lower. We don't even know if sigma-1 is responsible for the effects observed, but it wouldn't make sense to give someone Fluoxetine instead of Fluvoxamine (which is also widely available), especially when it would require overdose levels of Fluoxetine to achieve similar sigma-1 effects. More numbers available in the full text here: https://pubmed.ncbi.nlm.nih.gov/24508523/ https://pubmed.ncbi.nlm.nih.gov/24508523/

WalterSear 6y ago

It's suspected to be a specific side effect, not a part of the reuptake inhibition.

xkcd-sucks 6y ago

Generally speaking, "SSRI" is an ideal goal which isn't perfectly realized; all drugs in that class bind "off-target" to proteins other than SERT. In this case, fluvoxamine pharmacology is pretty clean and there is experimental evidence only for binding to sigma-1 receptor in addition to SERT (also to a whole bunch of CYP enzymes). Unfortunately the function of sigma-1 is not well understood but it affects calcium signalling in intracellular compartments where covid-19 replicates