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Re: Vraylar undopaminergic

Posted by SLS on October 12, 2020, at 22:12:40

In reply to Re: Vraylar SLS, posted by undopaminergic on October 12, 2020, at 0:35:21

> > I was interested in Vraylar because it the ratio of D3/D2 binding is significantly higher than Abilify.
> >
>
> That is its unique property, and the main one why I was interested in trying it too. That said, blocking dopamine D3 is not necessarily a good idea -- possibly even the opposite. Pramipexole, a D3 *agonist* was the only drug that ameliorated my anhedonia.
>
> -undopaminergic
>

Abilify and Vraylar bind to D3/D2 receptors, but they are not full antagonists. They are partial agonists. When Abilify first appeared, Stephen Stahl characterized it a dopamine system stabilizer.

1. High dopamine in the synaptic cleft -> receptors are antagonized.

2. Low dopamine in the synaptic cleft -> receptors are stimulated.

It sounds weird, but I imagine there is some kind of conformational change in the receptor at high versus low dopamine concentrations. The postsynaptic dopamine receptor actually has two distinct states that have different binding affinities. This might explain the dual action of partial agonists.


- Scott


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I dream of things that never were and ask why not.

The only thing necessary for the triumph of evil is that good men do nothing.

 

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URL: http://www.dr-bob.org/babble/20200711/msgs/1112279.html