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Re: 40% down to 25% -- Viibryd trial question » zonked

Posted by SLS on September 22, 2011, at 7:04:55

In reply to Re: 40% down to 25% -- Viibryd trial question » SLS, posted by zonked on September 21, 2011, at 22:03:53

> In another post, you mentioned a good question:
>
> Since both Viibryd and Abilify are partial 5HT1A agonists, how would this affect receptor occupancy?
>
> Have you found the answer to this question?

No. I think IC50 means the concentration at which 50% of the receptors are occupied and inhibited. The answer to the question is deceptively complicated. I've got a model floating around in my head, but it is difficult to explain briefly. One important question is to what degree these two drugs flip conformations to produce 5-HT1a agonism at a given receptor.

Questions like these are sometimes more esoteric than applicable. I think I would rather try Viibryd in ignorance and without predicting its potential to improve my condition. I might have an easier time suggesting answers to the questions asked once I establish how Viibryd affects me. I might even try removing Abilify if I respond well to the addition of Viibryd. Is D2 partial agonism important to the ability of Abilify to provide improvements in depression? Is 5-HT1a partial agonism sufficient? Remember, the most ubuquitous serotonin receptor in the brain is 5-HT1a. They populate numerous different regions and have different functions. Do Abilify and Viibryd mirror one another in the agonism of 5-HT1a receptor populations? I think Abilify is limited to somato-dendrytic autoreceptors. In addition to these receptors, Viibryd effectively acts upon inhibitory presynaptic autoreceptors and excitatory postsynaptic receptors, with it acting selectively on presynaptic autoreceptors, particularly at low dosages.

> Wikipedia reports the following:
>
> Vilazodone, 5HT1a :
> IC50 = 0.5 nM; IA = ~60-70%
>
> Aripiprazole, 5HT1a:
> Ki = 1.65 nM

Apples to oranges. I don't know how one would use these numbers to compare the two drugs.

Good morning.


- 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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