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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 6 of 6. This is the beginning of the thread.
Posted by conundrum on February 26, 2010, at 8:36:11
In reply to Re: Tricyclic most like SNRIs?, posted by bleauberry on February 22, 2010, at 19:57:23
Taken from the following study:
http://cat.inist.fr/?aModele=afficheN&cpsidt=2585906
"Duloxetine (5.0 mg/kg, s.c.) and fluoxetine (10.0 mg/kg, s.c.) increased dialysate levels of DA (65 and 60% vs. basal values, respectively), NAD (400 and 90%, respectively), and 5-HT (130 and 110%, respectively) in the frontal cortex (FCX)."
If I'm interpreting this correctly Duloxetine increases norepinephrine more than serotonin or dopamine in the PFC. Perhaps this isn't true through out the brain but it probably has clinical significance.
Posted by Brainbeard on February 26, 2010, at 8:36:11
In reply to Re: Tricyclic most like SNRIs? » bleauberry, posted by conundrum on February 22, 2010, at 22:23:18
Yes, and adding buspirone (Buspar) to either duloxetine (Cymbalta) or Prozac further elevates noradrenaline and dopamine levels, as seen from this very same study. We have to keep in mind though that it's a study of the RAT brain.
Posted by conundrum on February 26, 2010, at 8:36:11
In reply to Re: Tricyclic most ..... - Adding Buspar And Rats, posted by Brainbeard on February 23, 2010, at 8:49:12
> Yes, and adding buspirone (Buspar) to either duloxetine (Cymbalta) or Prozac further elevates noradrenaline and dopamine levels, as seen from this very same study. We have to keep in mind though that it's a study of the RAT brain.
True but my point was that despite higher ratio for 5HT to NE it still increased NE a lot in the rat PFC. It increased it 400% compared to the 130% in serotonin. I'm sure that varies in other parts in the brain and in humans, but I'm just trying to point out it may have a clinical effect for some.
Posted by Brainbeard on February 26, 2010, at 8:36:11
In reply to Re: Tricyclic most ..... - Adding Buspar And Rats » Brainbeard, posted by conundrum on February 23, 2010, at 14:04:07
> True but my point was that despite higher ratio for 5HT to NE it still increased NE a lot in the rat PFC. It increased it 400% compared to the 130% in serotonin. I'm sure that varies in other parts in the brain and in humans, but I'm just trying to point out it may have a clinical effect for some.
You're right. Duloxetine might have some other mechanism besides NRI through which it raises NE..
Posted by bleauberry on February 26, 2010, at 8:36:11
In reply to Re: Tricyclic most like SNRIs? » bleauberry, posted by conundrum on February 22, 2010, at 22:23:18
> Taken from the following study:
>
> http://cat.inist.fr/?aModele=afficheN&cpsidt=2585906
>
> "Duloxetine (5.0 mg/kg, s.c.) and fluoxetine (10.0 mg/kg, s.c.) increased dialysate levels of DA (65 and 60% vs. basal values, respectively), NAD (400 and 90%, respectively), and 5-HT (130 and 110%, respectively) in the frontal cortex (FCX)."
>
> If I'm interpreting this correctly Duloxetine increases norepinephrine more than serotonin or dopamine in the PFC. Perhaps this isn't true through out the brain but it probably has clinical significance.
>
>
>This can be deceiving. There is comparison to only one other drug. Both happen to be Ely Lilly drugs? See where I'm going? But that's just a small part of it.
There is no comparison to a variety of other drugs. So we can't really put these results into perspective.
The rat brain is in many ways different than the human brain. Well, obviously, no brain on the planet is like a human brain. To automatically assume that what a psychiatric drug does to a rat's brain chemicals will do the exact same thing to a human is, well, probably not accurate.
What happened to those initial peaks of NE the next day, a week later, a month later? We don't know. All we know is what a single dose did. We don't know how the brain adapted to that afterwards with chronic usage. Only with acute usage. Did the NE stay high, or did it restabilize to baseline, or did it go lower? We don't know. Even if we did, what does it mean? Nothing. All that matters is how the patient feels, and that cannot be predicted by how much of any brain chemical there is.
I'd say those doses were pretty darn potent for a little rat. So that's a bit misleading.
Interesting though.
Even though Savella is a serotonin and norepinephrine reuptake inhibitor with approximately equal affinity for both, why is it that after chronic usage NE stays elevated but serotonin doesn't? Things just aint that simple, ya know?
There's a lot we don't know. About the best it says is that there is a probability of getting a NE spike if you take a single dose. I have indeed felt that from cymbalta, and liked it, but it was gone by the 4th day of dosing and instead turned into suicidal feelings. So what happened? We don't know.
I think this study got off to a good start but didn't go far enough for useful results.
Posted by conundrum on February 26, 2010, at 8:36:12
In reply to Re: Tricyclic most like SNRIs?, posted by bleauberry on February 24, 2010, at 19:26:52
> There's a lot we don't know. About the best it says is that there is a probability of getting a NE spike if you take a single dose. I have indeed felt that from cymbalta, and liked it, but it was gone by the 4th day of dosing and instead turned into suicidal feelings. So what happened?Thats interesting. I wonder if it was from the sudden drop of NE or because SRI alone makes you feel suicidal or both.
> I think this study got off to a good start but didn't go far enough for useful results.
For sure.
This is the end of the thread.
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