6 ms·

The drug: https://en.wikipedia.org/wiki/Viloxazine https://en.wikipedia.org/wiki/Viloxazine tl;dr: It's an SNRI, like Effexor or Cymbalta.

goodells 6y ago
> It is a racemic compound with two stereoisomers, the (S)-(–)-isomer being five times as pharmacologically active as the (R)-(+)-isomer.[14] I can't wait until 2041 when this is phased out and we get "esviloxazine" for $300+/month.
PragmaticPulp 6y ago
> tl;dr: It's an SNRI, like Effexor or Cymbalta. The mechanism of action section specifically says that it did not block norepinephrine reuptake in the studied brains of rats (only in heart tissues) and that the serotonin reuptake inhibition was very weak. The mechanism of action is more complex, involving 5-HT2B antagonism and 5-HT2C agonism and some downstream upregulation of GABA-B in certain brain areas. It's likely there are additional mechanisms that are not fully understood yet. tl;dr: It's nothing like an SNRI like Effexor or Cymbalta. Always defer to actual patient outcomes in clinical studies instead of trying to infer a drug's effects based on binding affinities.
- NeutronStar 6y ago
  > It is a selective norepinephrine reuptake inhibitor (NRI).[1] From the first paragraphe on wikipedia...
- lazide 6y ago
  It’s a real shit show is what it is. If you compare those side effects the ACTUAL side effects of stimulants in kids and adults with ADHD (for instance, it reduces drug dependency, addiction, hyperactivity in ADHD folks while having the opposite effect on those who do not have ADHD), it’s clear this should be unethical to prescribe for anyone stimulants would be effective on. The only reason it even really comes up is the OMG stimulants are evil crowd who don’t want to even look at the reality of the situation.
  - PragmaticPulp 6y ago
    Please don't try to guess treatment outcomes based on binding affinities. > it’s clear this should be unethical to prescribe for anyone stimulants would be effective on. This is wrong in so many ways. Again, please don't try to guess outcomes based on binding affinities. For what it's worth, some of the non-stimulant ADHD medications such as Guanfacine are strikingly effective for ADHD when titrated properly, some times even moreso than traditional stimulants. The challenge is that titration can take time and the effects are not immediately apparent from the first dose, whereas stimulant medication follows the opposite trajectory where the first dose is the most effective and subsequent dosing has reduced effects due to tolerance. Parents often mistake the instant response of stimulants for superior efficacy in treating ADHD, whereas instrumented tests show that medications like Guanfacine are actually quite good if the patient is given time to adapt.
    - The_rationalist 6y ago
      Are there long term comparative studies? Any reference benchmarck?
    - astrange 6y ago
      I actually moved off guanfacine and onto Strattera because it has so many side effects - for instance, it makes you very weak to alcohol and it affects your heart rate. It's also physiologically addictive and you have to ramp off it for a week or two, which is a problem if you've forgotten to get a refill since, you know, you have ADHD. Ironically these are all things people think Adderall does which it doesn't do.
    - lazide 6y ago
      I wasn’t guessing outcomes based on binding affinities, I was going off the data they posted in the article AND multiple large controlled studies on stimulants in ADHD populations. For instance - stimulants in ADHD populations do not cause suicidal ideation. Which is nice. This drug does for a non trivial number of folks who get it.
- Daho0n 6y ago
  This sounds very good until you actually read the fact that is or has been sold as an antidepressant.
comp_throw7 6y ago
My first thought when I read the list of side effects was "this sounds like a bit like an antidepressant". Then I saw (from the original AP article) that it was, in fact, originally marketed as an antidepressant in Europe.
The_rationalist 6y ago
Amphetamine stimulants are SNRI too just like some antidepressants such as Wellbutrin. What I do not understand is: they have the same mechanism of action (or at least the same consequence) but the effect is different, one mostly focus on fixing ADHD symptoms and one mostly focus on depression. What explain such a difference in behavior? BTW unrelated but simultaneously taking SSRIs with stimulants show great results (but there are few studies) (of course don't overdose if you don't want serotonine syndrome)
- refurb 6y ago
  Amphetamines cause the release of norepinephrine as a major component of their effect.
  - The_rationalist 6y ago
    Yes just like SNRIs antidepressants so what is the difference? (stimulants also are dopamine reuptake inhibitors and low serotonine reuptake inhibitor) And no it does not cause the release of any monoamine, when they are released they can stay longer in the brain before being garbage collected which virtually increase their density. It is an unknown whether delayed this garbage collection cycle accelerate ageing or other side effects.
    - refurb 6y ago
      No, sympathomimetics like amphetamines cause neurotransmitter release in addition to be reuptake inhibitors.
      - The_rationalist 6y ago
        Doesn't induced neurotransmitter release lead to tolerance up to the point that the benefits 100% cancels out?
    - pseudalopex 6y ago
      The drugs you're talking about are classified NDRIs not SNRIs. Amphetamine is a releasing agent too. Different drugs have different receptor affinities. And the different metabolites do too.

goodells 6y ago

> It is a racemic compound with two stereoisomers, the (S)-(–)-isomer being five times as pharmacologically active as the (R)-(+)-isomer.[14] I can't wait until 2041 when this is phased out and we get "esviloxazine" for $300+/month.

PragmaticPulp 6y ago

> tl;dr: It's an SNRI, like Effexor or Cymbalta. The mechanism of action section specifically says that it did not block norepinephrine reuptake in the studied brains of rats (only in heart tissues) and that the serotonin reuptake inhibition was very weak. The mechanism of action is more complex, involving 5-HT2B antagonism and 5-HT2C agonism and some downstream upregulation of GABA-B in certain brain areas. It's likely there are additional mechanisms that are not fully understood yet. tl;dr: It's nothing like an SNRI like Effexor or Cymbalta. Always defer to actual patient outcomes in clinical studies instead of trying to infer a drug's effects based on binding affinities.

NeutronStar 6y ago
> It is a selective norepinephrine reuptake inhibitor (NRI).[1] From the first paragraphe on wikipedia...
lazide 6y ago
It’s a real shit show is what it is. If you compare those side effects the ACTUAL side effects of stimulants in kids and adults with ADHD (for instance, it reduces drug dependency, addiction, hyperactivity in ADHD folks while having the opposite effect on those who do not have ADHD), it’s clear this should be unethical to prescribe for anyone stimulants would be effective on. The only reason it even really comes up is the OMG stimulants are evil crowd who don’t want to even look at the reality of the situation.
- PragmaticPulp 6y ago
  Please don't try to guess treatment outcomes based on binding affinities. > it’s clear this should be unethical to prescribe for anyone stimulants would be effective on. This is wrong in so many ways. Again, please don't try to guess outcomes based on binding affinities. For what it's worth, some of the non-stimulant ADHD medications such as Guanfacine are strikingly effective for ADHD when titrated properly, some times even moreso than traditional stimulants. The challenge is that titration can take time and the effects are not immediately apparent from the first dose, whereas stimulant medication follows the opposite trajectory where the first dose is the most effective and subsequent dosing has reduced effects due to tolerance. Parents often mistake the instant response of stimulants for superior efficacy in treating ADHD, whereas instrumented tests show that medications like Guanfacine are actually quite good if the patient is given time to adapt.
  - The_rationalist 6y ago
    Are there long term comparative studies? Any reference benchmarck?
  - astrange 6y ago
    I actually moved off guanfacine and onto Strattera because it has so many side effects - for instance, it makes you very weak to alcohol and it affects your heart rate. It's also physiologically addictive and you have to ramp off it for a week or two, which is a problem if you've forgotten to get a refill since, you know, you have ADHD. Ironically these are all things people think Adderall does which it doesn't do.
  - lazide 6y ago
    I wasn’t guessing outcomes based on binding affinities, I was going off the data they posted in the article AND multiple large controlled studies on stimulants in ADHD populations. For instance - stimulants in ADHD populations do not cause suicidal ideation. Which is nice. This drug does for a non trivial number of folks who get it.
Daho0n 6y ago
This sounds very good until you actually read the fact that is or has been sold as an antidepressant.

comp_throw7 6y ago

My first thought when I read the list of side effects was "this sounds like a bit like an antidepressant". Then I saw (from the original AP article) that it was, in fact, originally marketed as an antidepressant in Europe.

The_rationalist 6y ago

Amphetamine stimulants are SNRI too just like some antidepressants such as Wellbutrin. What I do not understand is: they have the same mechanism of action (or at least the same consequence) but the effect is different, one mostly focus on fixing ADHD symptoms and one mostly focus on depression. What explain such a difference in behavior? BTW unrelated but simultaneously taking SSRIs with stimulants show great results (but there are few studies) (of course don't overdose if you don't want serotonine syndrome)

refurb 6y ago
Amphetamines cause the release of norepinephrine as a major component of their effect.
- The_rationalist 6y ago
  Yes just like SNRIs antidepressants so what is the difference? (stimulants also are dopamine reuptake inhibitors and low serotonine reuptake inhibitor) And no it does not cause the release of any monoamine, when they are released they can stay longer in the brain before being garbage collected which virtually increase their density. It is an unknown whether delayed this garbage collection cycle accelerate ageing or other side effects.
  - refurb 6y ago
    No, sympathomimetics like amphetamines cause neurotransmitter release in addition to be reuptake inhibitors.
    - The_rationalist 6y ago
      Doesn't induced neurotransmitter release lead to tolerance up to the point that the benefits 100% cancels out?
  - pseudalopex 6y ago
    The drugs you're talking about are classified NDRIs not SNRIs. Amphetamine is a releasing agent too. Different drugs have different receptor affinities. And the different metabolites do too.