Aripiprazol and the brain

[mb-909]

How can it be that a known substance is perscribed to even teenagers if there is no evidence how it really works (even Wikipedia doesn't userly know how it works, partial agonist or something else?)? It baffles me that even after long research I couldn't find any useful information about this substance. Neuroleptics tend to decrease the michondrias in brain cells, resulting in faster cell death, at least in rats. This might be a reason for brain shrinkage, since the cells don't have to produce the amount's of dopamin as usual and are shutting down therefor.

I have been on these medication for 7 weeks and 8 weeks have passed since my last dose. I still feel the changes in my brain and my body from withdrawal. This is the reason why I started to inform myself over all kind of drugs and the mechanismn of work, but I can't find any useful studies in that kind of regard (my anxienity disorder kind of suck, but yeah, I have to deal with it any way). I would be really grateful if somebody could light me up 8). (By the way: Do you think that these medications are more toxic than illicit drugs, because they are used daily over long periods of time?)

 

[St3ve]

The general idea is that in psychosis/schizophrenia there's an excess of dopamine in some of the brain's main dopamine pathways, whereas in other pathways there is not enough dopamine. Traditional anti-psychotics work by blocking the D2 receptor, this fixes the issue of excess dopamine but does not fix the issue of pathways where there isn't enough dopamine. This causes side effects.

Aripiprazole is different in that it functions as a partial agonist. This means it binds to the same receptors dopamine binds to, but doesn't fully activate them. In a dopamine pathway where there is a lot of dopamine, aripiprazole will compete for binding to receptors with dopamine, but it's less effective at activating them than dopamine. The net result is that you decrease overall activity in hyperactive pathways. In pathways where there is very little dopamine, competition will be less and aripiprazole is free to bind to the receptors, resulting in a net increase in activity there. Overall this should lead to "rebalancing" of the brain's dopamine pathways and fix many of the symptoms (though not all) of psychosis.

Prescribed medications generally should be safer than most illicit substances (especially new research chemicals). All pharmaceutical substances have to go through a very rigorous preclinical and clinical testing phase in which their usefulness, side effects and toxicity are evaluated. Sometimes certain toxic effects are missed, leading to the drug being withdrawn from the market at a later point. This is rather rare though, and most pharmaceuticals can be regarded as "safe".

 

[mb-909]

Sounds ok to me. The thing is that neuroleptics tend to decrease brain volume over time. That was the reason why I quit. I still have nasty tremors and headaches, which are probably withdrawal symptoms. Are these symptoms created trough a dopamin overflow or through missing dopamin? Is it likely that the mychondrias in the brain cells are reduced, because of less activity and less dopamin production? Since I didn't have the classic psychosis (severe depression), a lessened dopamin system would be counterproductive wouldn't it?

 

[Jonneh]

Nice explanation St3ve. I've always thought of partial agonists as the Marxists of the nervous system, to each according to his needs and all that. GABA antagonists are the capitalists, I suppose.

 

[phatass]

sory to derail a bit, but could anyone enlighten me on the interaction(s) between aripiprazole and methylphenidate....?

Thanks

 

[mb-909]

There shouldn't be any major drug interactions between these 2 substances. If you go after pharmacodynamics there should be 2 druginteractions. Both are split up over CYP2D6 in your liver, which could result in higher plasma levels for a longer period of time. Dextroamphetamine and Abilify didn't seem to interact and therefor it shouldn't interact with Methylphendiate. Abilify and meth showed to increase the positive noticeable effects of the rush, which is the reason why it shouldn't be used for addicts. The thing, which I don't understand, is the partial agonist mechanismn. The explanation above is what I understand, but some of the druginteractions with Abilify don't make sense, which is the reason why I opened this thread...

My main concern is the gray brain matter (which can't regenerate that easily, or not at all), which seems to be lost over time.The loss in Haldol treaties can be extreme as 2.4% over the first year and 1% for Clozapin treaties. After that the process is slowing down. This is my concern, since Abilify is also a neuroleptic. But still everybody says it is no concern... Haldol was said to be safe in the past, too. In the end we are genuia pigs.

 

[mb-909]

"Following the acute phase of treatment for positive symptoms, there may be unmasking of negative symptoms which are conventionally associated with reduced frontal lobe volume and less amenable to treatment.92,93 Taken together, antipsychotic drugs may unmask or even induce negative symptoms which are in turn related to cerebral gray matter loss especially in the first year. These findings indicate that the early phase of treatment deserves fuller exploration to determine how the balance of symptom control and cerebral gray matter integrity can be optimized in the first episode of schizophrenia. "

http://schizophreniabulletin.oxfordjournals.org/content/37/1/199.full

and here is a paper about the first weeks of neuroleptic treatment... (PDF)... up to 1.9 % loss in the first year of treatment...

https://www.google.de/url?sa=t&rct=...UzwkEs1fGbIx5pA&bvm=bv.80642063,d.bGQ&cad=rja


I am just sceptical and always look for the worst outcome. ^^