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Re: Abilify and dopamine release » SLS

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


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URL: http://www.dr-bob.org/babble/20120718/msgs/1022358.html