31 replies to this topic

[FW900]

 

 

Yes jason but what about theh MAIN THING - TOLERANCE ?  

Most people report tolerance with phentropil and tianpetine and suddenly it stops working ....if this happens can something be done to reverse the tolerance ?

 

 

 

Upregulation is typically the result of tolerance (a substance, decreases the amount of a NT, usually via antagonism is causing your brain to increase the density of receptors in a given region to compensate).

 

It doesn't matter it "stops working" you are trying to induce dopamine upregulation, you aren't taking them for their effects. You will get tolerance to the drugs' effects but as long as you are taking it, dopamine receptors in theory should upregulate by compounds known to cause it.

 

But effects are direct result of dopamine up-regulation .. If D receptors up-regulate = Reversal of emotional mood blunting . so as long as the receptors are up-regulated the reversal "effect" should be permanent as well 

 

 

Forex, I'll try to explain this the best I can with some examples. This is a tough topic to understand.

 

The brain's response to a compound in lamest terms is to either increase or decrease the density of receptors being acted upon as a rough way of trying to maintain a complex neurological homeostasis.

 

Take amphetamine for instance, most affected dopamine (sub)receptors will decrease in density (downregulate) in response to the excess dopamine caused mostly by amphetamine's action as a dopamine releasing agent. The downregulation is responsible for the perceived tolerance as it no longer yields the same subjective effects as it once did.

 

Now, look at the opposite scenario; what happens when receptors upregulate? Let's use phenylpiracetam as an example. Likely it acts as an antagonist on certain NT receptors. The response is to increase the density of these receptors (upregulate). After a while, people may get used to phenlypiracetam and they feel it doesn't work anymore (likely due to to downregulation of alpha7NAChr but this is another matter). This does not mean that upregulation is not occurring. The development if upregulation is mostly always the result of tolerance. Just because these drugs no longer have any effect, or even if they begin to have adverse effects, does not mean upregulation is not taking place.

 

Typically, NT receptors take a weeks to significantly change in density, and will more or less be semi-permanent. With continued abstinence typically, even upregulated receptors will decrease in density. The notion of "permanent" upregulation is erroneous (interestingly enough, NMDAr is very different, I believe there are studies with MK-801, showing that downregulated receptors never return to homeostasis).

 

Theoretically, you may well benefit from dopamine receptor upregulation, but you would not notice it immediately as it is a process that takes a while. Likewise, it is a process that would take a while to go away also.

Edited by FW900, 02 December 2014 - 07:34 AM.

[forexworld12]

 

 

 

Yes jason but what about theh MAIN THING - TOLERANCE ?  

Most people report tolerance with phentropil and tianpetine and suddenly it stops working ....if this happens can something be done to reverse the tolerance ?

 

 

 

Upregulation is typically the result of tolerance (a substance, decreases the amount of a NT, usually via antagonism is causing your brain to increase the density of receptors in a given region to compensate).

 

It doesn't matter it "stops working" you are trying to induce dopamine upregulation, you aren't taking them for their effects. You will get tolerance to the drugs' effects but as long as you are taking it, dopamine receptors in theory should upregulate by compounds known to cause it.

 

But effects are direct result of dopamine up-regulation .. If D receptors up-regulate = Reversal of emotional mood blunting . so as long as the receptors are up-regulated the reversal "effect" should be permanent as well 

 

 

Forex, I'll try to explain this the best I can with some examples. This is a tough topic to understand.

 

The brain's response to a compound in lamest terms is to either increase or decrease the density of receptors being acted upon as a rough way of trying to maintain a complex neurological homeostasis.

 

Take amphetamine for instance, most affected dopamine (sub)receptors will decrease in density (downregulate) in response to the excess dopamine caused mostly by amphetamine's action as a dopamine releasing agent. The downregulation is responsible for the perceived tolerance as it no longer yields the same subjective effects as it once did.

 

Now, look at the opposite scenario; what happens when receptors upregulate? Let's use phenylpiracetam as an example. Likely it acts as an antagonist on certain NT receptors. The response is to increase the density of these receptors (upregulate). After a while, people may get used to phenlypiracetam and they feel it doesn't work anymore (likely due to to downregulation of alpha7NAChr but this is another matter). This does not mean that upregulation is not occurring. The development if upregulation is mostly always the result of tolerance. Just because these drugs no longer have any effect, or even if they begin to have adverse effects, does not mean upregulation is not taking place.

 

Typically, NT receptors take a weeks to significantly change in density, and will more or less be semi-permanent. With continued abstinence typically, even upregulated receptors will decrease in density. The notion of "permanent" upregulation is erroneous (interestingly enough, NMDAr is very different, I believe there are studies with MK-801, showing that downregulated receptors never return to homeostasis).

 

Theoretically, you may well benefit from dopamine receptor upregulation, but you would not notice it immediately as it is a process that takes a while. Likewise, it is a process that would take a while to go away also.

 

thanks for the detailed response man 

 

A lot of information is quite hard to comprehend ,but I  believe if the receptors up-regulate - The effects should be felt directly . you can't have upregulation happening place and don't feel the effect 

 

 I get that upregulation doesn't cause tolerance but downregulation does so that is why things like ritalin stops working -BUT I do not understand  what if ritalin is given to a person like me (ahnedonia - downregulated receptor) My best guess is It will result in reversal of Post ssri sexual dysfunction and reverse the  ahnedonia/depression SHORT TERM (drug life) 

Like Say Dopamine agonist - most of them reverses Ahnedonia/depression and PSSD ... but after a week the effects fade away 

 

So it like when a DA or Ritalin is given to someone with a down-regulated receptor - it Up-regulates them short term - but ultimately Down-regulates which results in tolerance !  -

 

so what if We add something like phenylpiracetam or CDP choline or selegiline to ritalin or Dopamine agonist ...  In theory wouldn't it Reverse tolerance?.... in this case since +  ritalin charges/stimulates the dopamine receptors that decreases in density but at the same time Up-regulation is taking place with cdp-choline or selegiline etc

 

 

I just read about  Dextroamphetamine.. It states that "Dextroamphetamine  is used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy, and is sometimes prescribed off-label for its past medical indications, such as depression, obesity, and nasal congestion.^[10][11] Long-term amphetamine exposure in some animal species is known to produce abnormal dopamine system development or nerve damage,^[12][13] but, in humans with ADHD, amphetamines appear to improve brain development and nerve growth.^[14][15][16] Magnetic resonance imaging studies suggest that long-term treatment with amphetamine decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function in several parts of the brain, such as the right caudate nucleus"

Edited by forexworld12, 04 December 2014 - 06:18 PM.