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Re: Abilify and dopamine release » TRD_12

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


Some see things as they are and ask why.
I dream of things that never were and ask why not.

- George Bernard Shaw

 

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