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Why is drugs specific to areas of the brain, why dont they affect whole brain?

net-protein atomoxetine strattera sert-protein dat-protein

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#1 the_apollo

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Posted 11 August 2014 - 04:38 PM


I got a kinda trycky question about drugs action on specific areas of the brain;

 

Take for example the NET-protein, handles reuptake of norepinephrine and in some areas also dopamin, the protein is expressed in many areas of the brain,

it (to me anyway) looks to be identical in all areas of the brain, but for some reason which i cannot find why, drugs dont inhibit the NET-protein in all areas of the brain, only specific.

 

    An example would be the NET-inhibitor (NRI) Atomoxetine, brand name 'Strattera', it is used to treat ADHD which it does by inhibiting the NET-protein in the prefrontal cortex,

  it does not seem to change NET-activity in say striatum, temporal cortices or any other area..

 

I've looked and seached the internet for clues, it may even be a simple answer to it, but i just cant find it..

 

Another thought i had about this is that reuptake inhibitors in general seems to be specific to areas, be it serotonin, noradrenaline or dopamine reuptake inhibitors,

they seem to only affect a certain area of the brain,

sometimes even lateralized, meaning on side or the other of the brain.

 

 

It may sound fuzzy, so please,

if you have question about what i mean, just question!


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#2 Tom_

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Posted 12 August 2014 - 10:23 AM

This isn't true. Re-uptake inhibitors do effect all areas that make use of that neurotransmitter.

 

One wouldn't expect to find much increased activity in the striatum with an NRI because its primairly regulated by dopamine.

 

Most of the studies looking at the effects of Atomoxetine on the brain will be looking at areas associated with ADHD and this is likely why you can't find any studies about increase activity of noradrenaline from Atomoxetine in anywhere apart from the pre-frontal cortex.

 

You should also be aware that almost all drugs have other mechanisms of action which are not talked about because of irrelevence to their main treatment target or because they are weak. For example the well known SSRI Fluoxetine actually has significant 5HT2c antagonist effects which increase noradrenergic and dopaminergic activity in the pre-frontal cortex and these extra MOA's can be a reason a drug seems to have a particually strong effect in one area.


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#3 Flex

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Posted 12 August 2014 - 01:20 PM

Thats a good question Apollo.

 

Afaik Quetiapine or its metabolite affect only the NET in the PFC.

Amisulpride does not affect the Striatum or at least very weak, thats why it doesnt cause tardive dyskinesia.

 

I dont know the reasons behind that and want also to know why.

 

Btw: I really dont care if someone rates this post as: Needs refference or ill informed


Edited by Flex, 12 August 2014 - 01:22 PM.

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#4 Tom_

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Posted 12 August 2014 - 01:27 PM

The effects of drugs that don't act only as re-uptake inhibitors can be fairly speific when acting as agonists of antagonists because different receptors are found in different areas of the brain. For example, D1 receptors are found almost exclusively in the PFC. So an agonist of D1 receptors with no other activity would only increase dopamine in the PFC and any other neurotransmitters that dopamine in the PFC effects. If another drug is given instead that acts as a SNRI you will see increases of serotonin and noradrenaline accross the brain but you would also see for example an increase in dopamine in the PFC as alpha 2 receptors act as autoreceptors on dopaminergic neurones within the PFC.



#5 Flex

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Posted 12 August 2014 - 01:39 PM

No, look at this:

Comparison of the distributions of D1 and D2 dopamine receptor mRNAs in rat brain.

http://www.ncbi.nlm..../pubmed/1839499



#6 Tom_

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Posted 12 August 2014 - 01:49 PM

First of all mRNA does not equal receptors (although there is of course a very strong correlation). Secondly the study doesn't paint an accurate picture of denesity of receptors but only gives a very general overview and thirdly its a rats brain, not a human one. They are the main weaknessess of the study I can see with only an abstract.

 

More importantly the study supports my view...I'm not sure of your point.



#7 Flex

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Posted 12 August 2014 - 02:07 PM

Ok next one:

http://www.nature.co...s/1380111a.html

 

Very high densities of D1-dopamine receptors were found particularly in the medial caudate nucleus, whereas D2-dopamine receptors were evenly distributed throughout the caudate. The densities of D1- and D2-dopamine receptors were similar in the caudate nucleus and the putamen, whereas there were 4 to 7 times higher densities of the D1- than of the D2-dopamine receptors in several limbic and neocortical regions. The receptor distribution in the autoradiographic study was consistent with that demonstrated in the living human brain using [11C]SCH 23390 and [11C]raclopride


Edited by Flex, 12 August 2014 - 02:08 PM.


#8 the_apollo

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Posted 12 August 2014 - 04:22 PM

This isn't true. Re-uptake inhibitors do effect all areas that make use of that neurotransmitter.

 

One wouldn't expect to find much increased activity in the striatum with an NRI because its primairly regulated by dopamine.

 

Most of the studies looking at the effects of Atomoxetine on the brain will be looking at areas associated with ADHD and this is likely why you can't find any studies about increase activity of noradrenaline from Atomoxetine in anywhere apart from the pre-frontal cortex.

 

You should also be aware that almost all drugs have other mechanisms of action which are not talked about because of irrelevence to their main treatment target or because they are weak. For example the well known SSRI Fluoxetine actually has significant 5HT2c antagonist effects which increase noradrenergic and dopaminergic activity in the pre-frontal cortex and these extra MOA's can be a reason a drug seems to have a particually strong effect in one area.

 

Actually, the effect of atomoxetine has been studied in other areas than just the prefrontal cortices, such as the striatum, but with no change in catecholamine activity.

 

 

In contrast to methylphenidate, atomoxetine did not increase DA in striatum or nucleus accumbens

http://www.ncbi.nlm....pubmed/12431845



#9 the_apollo

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Posted 14 August 2014 - 04:22 PM

Ok next one:

http://www.nature.co...s/1380111a.html

 

Very high densities of D1-dopamine receptors were found particularly in the medial caudate nucleus, whereas D2-dopamine receptors were evenly distributed throughout the caudate. The densities of D1- and D2-dopamine receptors were similar in the caudate nucleus and the putamen, whereas there were 4 to 7 times higher densities of the D1- than of the D2-dopamine receptors in several limbic and neocortical regions. The receptor distribution in the autoradiographic study was consistent with that demonstrated in the living human brain using [11C]SCH 23390 and [11C]raclopride

 

Interesting then, because i found a study detailing that both D1 and D2 receptor stimulation is necessary for full response of dopamine agonist, which of dopamine is an agonist of the receptors of course.

 

 

Stimulation of both D1 and D2 dopamine receptors appears necessary for full expression of postsynaptic effects of dopamine agonists:

http://www.ncbi.nlm..../pubmed/2880637


Edited by the_apollo, 14 August 2014 - 04:23 PM.


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#10 Flex

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Posted 14 August 2014 - 05:26 PM

Not to mention the effect of Cocaine on D1 receptors of Medium spiny Neurons in the Nucleus accumbens.



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#11 farshad

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Posted 09 August 2019 - 10:07 AM

I'm pretty sure most drugs that increase a receptor does so in all areas most of the time. It is difficult to make a drug only act in one specific area of the brain without affecting others and you would have to specifically design it that way.


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