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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 11 of 11. This is the beginning of the thread.
Posted by TRD_12 on July 29, 2012, at 8:32:11
Does anyone know in which dosing range Abilify releases most dopamine?
Thanks.
Posted by SLS on July 29, 2012, at 9:23:04
In reply to Abilify and dopamine release, posted by TRD_12 on July 29, 2012, at 8:32:11
> Does anyone know in which dosing range Abilify releases most dopamine?
That's a great question! I don't know!My guess:
At higher dosages, I imagine Abilify (aripiprazole) produces less of an increase in DA release than lower dosages. This might explain why so many people with depression to better at dosages of 2.0 - 5.0 mg/day rather than higher dosages.
Abilify is a unique drug among the neuroleptic antpsychotics (AP).
What I do know is that Abilify will produce a smaller increase in dopamine (DA) release than other APs. This is because Abilify is a DA receptor partial agonist. The rest are full antagonists. However, releasing more DA presynaptically does not produce a stimulating effect if the postsynaptic receptors are completely blocked and inhibited. Abilify binds to these same receptors, but does not completely inhibit them. Some researchers initially conceptualized Abilify as being a "dopamine system stabilizer". At low concentration of synaptic DA, Abilify acts predominantly as a postsynaptic receptor agonist. At higher concentrations of DA, it acts as an antagonist. In addition, Abilify acts as a partial agonist at serotonin 5-HT1a receptors, a mechanism that might actually increase DA release some brain structures.
"Intraperitoneal injection of aripiprazole (0.5mg/kg) increased dopamine release in mPFC without affecting those in aVTA, pVTA, or NAc, whereas 10mg/kg decreased the release in all four regions."
http://www.ncbi.nlm.nih.gov/pubmed/21925189
The amount of Abilify used per body weight in this study is much higher than what is used for human application. I don't know how relevant the results are. The numbers do demonstrate a trend, though.
- Scott
Posted by Phillipa on July 29, 2012, at 9:57:26
In reply to Re: Abilify and dopamine release » TRD_12, posted by SLS on July 29, 2012, at 9:23:04
Being ignorant in psychopharmacology. I just don't see how an atypical antipsychotic could be effective as an antidepressant. All the google searches always pull up it being used for psychosis? Phillipa
Posted by TRD_12 on July 29, 2012, at 10:02:04
In reply to Re: Abilify and dopamine release » TRD_12, posted by SLS on July 29, 2012, at 9:23:04
> That's a great question! I don't know!
>
> My guess:
>
> At higher dosages, I imagine Abilify (aripiprazole) produces less of an increase in DA release than lower dosages. This might explain why so many people with depression to better at dosages of 2.0 - 5.0 mg/day rather than higher dosages.
>
> Abilify is a unique drug among the neuroleptic antpsychotics (AP).
>
> What I do know is that Abilify will produce a smaller increase in dopamine (DA) release than other APs. This is because Abilify is a DA receptor partial agonist. The rest are full antagonists. However, releasing more DA presynaptically does not produce a stimulating effect if the postsynaptic receptors are completely blocked and inhibited. Abilify binds to these same receptors, but does not completely inhibit them. Some researchers initially conceptualized Abilify as being a "dopamine system stabilizer". At low concentration of synaptic DA, Abilify acts predominantly as a postsynaptic receptor agonist. At higher concentrations of DA, it acts as an antagonist. In addition, Abilify acts as a partial agonist at serotonin 5-HT1a receptors, a mechanism that might actually increase DA release some brain structures.
>
> "Intraperitoneal injection of aripiprazole (0.5mg/kg) increased dopamine release in mPFC without affecting those in aVTA, pVTA, or NAc, whereas 10mg/kg decreased the release in all four regions."
>
> http://www.ncbi.nlm.nih.gov/pubmed/21925189
>
> The amount of Abilify used per body weight in this study is much higher than what is used for human application. I don't know how relevant the results are. The numbers do demonstrate a trend, though.
>
>
> - Scott
>
>The high incidence of akathisia should point to a decrease in dopamine, but maybe it's only in a different circuit that is not involved in mood. I don't know. I know I had akathisia at 7.5mg, maybe I should have tried a lower dosage.
> What I do know is that Abilify will produce a smaller increase in dopamine (DA) release than other APs.
This is interesting, I did not know this. Maybe Seroquel at doses up 300mg produces the highest increase in dopamine of the AAPs?
/trd
Posted by TRD_12 on July 29, 2012, at 10:04:39
In reply to Re: Abilify and dopamine release » SLS, posted by Phillipa on July 29, 2012, at 9:57:26
> Being ignorant in psychopharmacology. I just don't see how an atypical antipsychotic could be effective as an antidepressant. All the google searches always pull up it being used for psychosis? Phillipa
Maybe you should try google "antipsychotic major OR unipolar depression"..
Posted by Phillipa on July 29, 2012, at 21:18:17
In reply to Re: Abilify and dopamine release » Phillipa, posted by TRD_12 on July 29, 2012, at 10:04:39
I have in past and don't see the atypicals being used. Exception is other mental health websites.
Posted by rjlockhart04-08 on July 29, 2012, at 21:27:09
In reply to Re: Abilify and dopamine release » TRD_12, posted by Phillipa on July 29, 2012, at 21:18:17
most nueroleptics act to reduce dopamine in certain areas of the brain that are associated with manic depressive and schizophrenia that cause abnormalites and bizarre behavior. They came out with newer antipsychotics the past 20 years....compazine, zyprexa, invega, latuda....and of course abilify. I see abilify commericals all the time on tv advertisements, they use the phrase "managing your depression" when its not even a antidepressant. But Abilify...it does have some kinda of mechanism to increase dopamine in %certain% areas of the brain. Most older meds directly blocked dopamine, and reduced activity. Zyprexa works with the 5HTP and dopamine receptors. Abilify some how does have a beneficial effect with dopamine and depression but still its known to block it and regulate it, not release it to my knowedge.
rj
Posted by TRD_12 on July 30, 2012, at 5:41:53
In reply to Re: Abilify and dopamine release » SLS, posted by Phillipa on July 29, 2012, at 9:57:26
>I just don't see how an atypical antipsychotic could be effective as an antidepressant.
The antidepressant properties of atypicals are not limited to what you see. They are effective at treating negative symptoms just as antidepressants. The difference is that when used to treat depression as opposed to psychosis, lower doses are used, where they do not block D2-receptors hard enough to reduce dopamine output.
Let's look at quetiapine e.g. which I take. The antagonism at 5HT2A-receptor releases dopamine output in certain brain areas, this is why no EPS is seen at virtually any dose and the low incidence of TD. This dopamine release can help relieve depression the same way Wellbutrin does. Furthermore, quetiapine blocks 5HT2C-receptors which should release both dopamine and noradrenaline, which could contribute to antidepressant actions and cognitive improvement.
Then we have partial agonism at 5HT1A receptors, the same action that Viibryd and Buspar exert, which is thought to mediate anxiolytic and antidepressant effects.
Antagonism at H1 is great for insomnia and anxiety. Quetiapine's metabolite norquetiapine has noradrenaline reuptake inhibiting properties (NET), same mechanism seen with Wellbutrin, nortriptyline, reboxetine, Effexor, Cymbalta etc. It increases noradrenaline, and dopamine to some extent.
Actions at 5HT6 and 5HT7 receptors can also have positive effects on mood, sleep and memory.
Antagonism at adrenergic alpha 2 receptors (and through alpha 1) releases noradrenaline and serotonin.As you can see, Seroquel hits a myriad of receptors and affects NE, DA and 5HT in one way or another. Just because a med is labeled an antipsychotic doesn't mean it can't have other uses, such as antidepressants, anxiolytics and hypnotics.
Lamictal seems to prevent dopamine depletion.
Sources:
Stahl's books
Wikipedia
http://www.ncbi.nlm.nih.govHope that helps,
trd
Posted by SLS on July 30, 2012, at 7:08:01
In reply to Re: Abilify and dopamine release » Phillipa, posted by TRD_12 on July 30, 2012, at 5:41:53
Thanks for the concise explanation!
I didn't know that Seroquel antagonized 5-HT2c receptors or acted as a partial agonist at 5-HT1a receptors. That's pretty cool. It explains a lot.
Seroquel made me feel somewhat dysphoric and irritable. Viibryd had no such affect on me. Perhaps it was the combination of NET inhibition and 5-HT2c antagonism that was responsible for my reaction. I never tried combining Prozac with desipramine. I wonder how I would have reacted to that.
I found this. Perhaps you already came across it:
http://www.ncbi.nlm.nih.gov/pubmed/20802307
- Scott
-----------------------------------
The antidepressant properties of atypicals are not limited to what you see. They are effective at treating negative symptoms just as antidepressants. The difference is that when used to treat depression as opposed to psychosis, lower doses are used, where they do not block D2-receptors hard enough to reduce dopamine output.Let's look at quetiapine e.g. which I take. The antagonism at 5HT2A-receptor releases dopamine output in certain brain areas, this is why no EPS is seen at virtually any dose and the low incidence of TD. This dopamine release can help relieve depression the same way Wellbutrin does. Furthermore, quetiapine blocks 5HT2C-receptors which should release both dopamine and noradrenaline, which could contribute to antidepressant actions and cognitive improvement.
Then we have partial agonism at 5HT1A receptors, the same action that Viibryd and Buspar exert, which is thought to mediate anxiolytic and antidepressant effects.
Antagonism at H1 is great for insomnia and anxiety. Quetiapine's metabolite norquetiapine has noradrenaline reuptake inhibiting properties (NET), same mechanism seen with Wellbutrin, nortriptyline, reboxetine, Effexor, Cymbalta etc. It increases noradrenaline, and dopamine to some extent.
Actions at 5HT6 and 5HT7 receptors can also have positive effects on mood, sleep and memory.
Antagonism at adrenergic alpha 2 receptors (and through alpha 1) releases noradrenaline and serotonin.As you can see, Seroquel hits a myriad of receptors and affects NE, DA and 5HT in one way or another. Just because a med is labeled an antipsychotic doesn't mean it can't have other uses, such as antidepressants, anxiolytics and hypnotics.
Lamictal seems to prevent dopamine depletion.
Sources:
Stahl's books
Wikipedia
http://www.ncbi.nlm.nih.gov
Posted by SLS on July 30, 2012, at 7:38:35
In reply to Re: Abilify and dopamine release » TRD_12, posted by SLS on July 30, 2012, at 7:08:01
> Lamictal seems to prevent dopamine depletion.
Do you have more information on this?
With regard to the dynamics of dopamine activity in the nucleus accumbens, I am guessing that it is increased by Lamictal through the disinhibition of DA circuits via thalamic glutamate release inhibition rather than by preventing some sort of "depletion". I don't think that it is depletion that reduces limbic hypoactivity. It is probably the result of some dysfunction upstream - perhaps a reduction in NE activity prefrontally. I don't really know. My pet theory might be wrong, but I haven't yet seen a better explanation for the dopaminergic properties of Lamictal.
http://www.dr-bob.org/babble/20080606/msgs/833971.html
I don't even know what is meant by "dopamine depletion". How does it occur?
- Scott
Posted by TRD_12 on July 30, 2012, at 9:37:44
In reply to Re: Abilify and dopamine release, posted by SLS on July 30, 2012, at 7:38:35
> > Lamictal seems to prevent dopamine depletion.
>
> Do you have more information on this?
>
> - ScottDisregard from that, it had to do with chemically induced dopamine depletion which could be prevented by lamotrigine.
What do you think about this:
"These results suggest that postsynaptic 5-HT1A receptors might be involved in the activity of lamotrigine."
From:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1160563/
"Enhancement of dopamine release in these areas may also play a major role in the antidepressant and anxiolytic effects seen upon postsynaptic activation of the 5-HT1A receptor."
From:
http://en.wikipedia.org/wiki/5-HT1A_receptorhttp://www.ncbi.nlm.nih.gov/pubmed/9109104
/trd
This is the end of the thread.
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