[jakeforpresident]

Hey all! long time no post...

I rather enjoyed the wiki article on Geodon http://en.wikipedia.org/wiki/Ziprasidone
and I suspect that rocknroll714 had something to do with this wiki's fine quality

I just have one small question; How quickly does ziprasidone dissociate from dopamine D2 receptors?

I've been seraching the net with no success...

 

[jonny neurotic]

I just discovered this stuff. I am ordering some straight away. I think it would augment the effects of aMT rather nicely. Already have some aMT in the post. The last time I tried it it was a bit too psychedelic for me. The serotonin 2A antagonism will combat that and the 2C antagonism will make things nicer for me. Also the d2 antagonism may serve to make it a more functional stim.

The only thing that bothers me is the alpha 1 antagonism. Perhaps some clonidine in the mix would balance that out a wee bitty. Heres hoping...

EDIT: Alpha 1 antagonism wont disinhibit noradrenaline like I though so clonidine wont be necessary in this mix...

 

[jonny neurotic]

http://en.wikipedia.org/wiki/Ziprasidone

Ziprasidone possesses affinity for and acts at the following receptors and transporters:

• D2 Antagonist (Ki = 4.8 nM)
• D3 Antagonist (Ki = 7.2 nM)
• 5-HT1A Agonist (Ki = 3.4 nM)
• 5-HT1D Antagonist (Ki = 2.3 nM)
• 5-HT2A Antagonist/Inverse Agonist (Ki = 0.4 nM)
• 5-HT2C (Ki = 1.3 nM)
• NET
• SERT
• H1 Antagonist (Ki = 47 nM)
• α1-adrenergic Antagonist (Ki = 10 nM)

http://www.theannals.com/content/36/5/839.short

Ziprasidone has demonstrated in vitro activity as a 5-HT(1A) receptor agonist and as a very weak inhibitor of serotonin and norepinephrine reuptake. These data do not support ziprasidone as being a clinically meaningful inhibitor of serotonin/norepinephrine reuptake.

http://informahealthcare.com/doi/abs/10.1517/13543784.4.4.291

Ziprasidone also exhibits appreciable affinity for dopamine D1 and D4 receptors (Ki = 32 and
40 nM, respectively)

 

[jonny neurotic]

So it has 10 fold selectivity for the D2 receptor over the D4 receptor. It has about as much effect at D4 as it does at the H1 receptor. Given the potency it has at the 5ht2A receptor the H1 and D4 antagonism will be negligible.

The D2 antagonism may potentiate(via presynaptic disinhibition) the dopaminaergic effects of aMT while preventing too much satisfaction/euphoria(post synaptically) and make it a more functional stim. The 5ht2C antagonism should also add to the dopaminergic qualities or at the very least prevent the serotonergic effects of the aMT from inhibiting dopamine too much.

The 5ht2A antagonism is the most prominent effect followed by the 5ht2c antagonism. The next most prominent effect is the antagonism of the 5ht1D receptor. The 5ht1D receptor "affects locomotion and anxiety. It also induces vascular vasoconstriction in the brain." So antagonism of this receptor should facilitate anxiolysis and increase blood flow to the brain. It also has a fairly high affinity for the 5ht1A receptor and the combined agonism from this and the aMT may be excessive. IDK if this will cause severe after effects. It may be worth throwing in an antagonist of this receptor for good measure. Something to think about.

The antagonism of the alpha1 adrenoceptor will disinhibit glutamatergic activity at the AMPA receptors in the temporal lobes, possibly giving a slight nootropic effect.

I am looking forward to trying this combo out...

 

[JohnG]

The antagonism of the alpha1 adrenoceptor will disinhibit glutamatergic activity at the AMPA receptors in the temporal lobes, possibly giving a slight nootropic effect.

Can you provide references for this ?

 

[jonny neurotic]

Can you provide references for this ?

http://www.ncbi.nlm.nih.gov/pubmed/19357950

...NE [] decreased glutamatergic excitatory post-synaptic currents (EPSCs) in all cortical layers. ...decrease of responses to pressure-application of AMPA...

But maybe this isn't such a good thing because;

We speculate that the decrease in temporal cortex excitability might promote a posterior-to-anterior shift in cortical activation together with a decrease in spontaneous background activity, resulting eventually in more effective sensory processing.

IDK...

 

[jonny neurotic]

Just got my ziprasidone today. I took 40mg just now because I have been taking aMT for the past three days and I am not getting the same effect from it so I plan on letting some receptors upregulate. The nice thing is that the 2C receptor will downregulate in response to the antagonistic effect so SA will be reduced. 2C activation in the basolateral amygdalae produces fear response and associated behaviour so blocking it and causing it to downregulate are both good things for SA.

 

[barry1685]

Just got my ziprasidone today. I took 40mg just now because I have been taking aMT for the past three days and I am not getting the same effect from it so I plan on letting some receptors upregulate. The nice thing is that the 2C receptor will downregulate in response to the antagonistic effect so SA will be reduced. 2C activation in the basolateral amygdalae produces fear response and associated behaviour so blocking it and causing it to downregulate are both good things for SA.

I don't understand how an antipsychotic helps with SA.

 

[JohnG]

I don't understand how an antipsychotic helps with SA.

They don't

 

[jonny neurotic]

I don't understand how an antipsychotic helps with SA.

If you read my other posts you would see that I am using this particular atipsychotic to augment the effects of aMT, which it does rather nicely. So far 7.5mg of aMT with 2 doses of 5mg of ziprasidone is a good combo. The ziprasidone must be taken with food but I think the aMT is best on an empty stomach.

 

[jonny neurotic]

I gave up on the aMT. Way too much tolerance happening too quickly. The ziprasidone on the other hand, is a keeper. It seems to work well for my SA but it needs something else to make it nice. I already mentioned what I intend to combine it with in another thread. It is OK at dose between 2-5mg. Higher than that it becomes drowsy. I don't take it every day only when I need to go where there are lots of people...

 

[barry1685]

I gave up on the aMT. Way too much tolerance happening too quickly. The ziprasidone on the other hand, is a keeper. It seems to work well for my SA but it needs something else to make it nice. I already mentioned what I intend to combine it with in another thread. It is OK at dose between 2-5mg. Higher than that it becomes drowsy. I don't take it every day only when I need to go where there are lots of people...

Doesn't antipsychotics block dopamine? How could this help you? I know that the goal of anti psychotics is to slow down rapid thoughts. But I'd rather have more dopamine than not having rapid thoughts.

 

[jonny neurotic]

Doesn't antipsychotics block dopamine? How could this help you? I know that the goal of anti psychotics is to slow down rapid thoughts. But I'd rather have more dopamine than not having rapid thoughts.

Read my earlier posts. The point is not to take this at high doses for a long enough time to cause upregulation of the dopamine receptors but to use it to modulate serotonin and my intention is to use this as and when required and not every day. Also at low doses D2 blockers increase dopamine output without blocking the effects to any great extent...

BTW, with Ki values the lower the number the higher the affinity for that receptor...