I was researching into cAMP due to taking forskolin lately and was surprised to see that high levels of cAMP shut down the prefrontal cortex. It seems that some or even all of the effect of norepinephrine and dopamine are due to their effect on cAMP.
It seems that NE attaches to the HCN via the alpha channel receptors and it signals the brain cells not to produce cAMP in the brain. DA modulates the sensitivity to cAMP which can indirectly cause more or less production of it.
It seems that the drug guanfacine, long used to treat ADD, works by mimicking what norepinephrine does to the prefrontal cortex. This opens up the cells and allows them to process information.
High levels of stress also build up cAMP in the brain so it's crucial to be as stress free as possible (most every ADDer had tons of stress).
So, guanfacine looks to be an excellent mental enhancer, especially if you have high blood pressure and lots of stress or if you use stimulants like adderall ritalin etc. which raise the blood pressure and (in some people) cause anxiety. Of course the bad side is that it can kill you, so it's very recommended to go to a dr at some point if you take this or at the least do extensive research until you're sure you know what the danger signs are. Also, you need to take it regularly or you are bound to give yourself problems. There's a long acting version in the works, but it will be expensive. The current version needs to be taken several times a day and lasts maybe 4-8 hours.
I've always thought that raw dopamine didn't make any sense at all as the mechanism for ADD symptom relief. It's actually super easy to up dopamine without adderall but it seems to give me only limited relief. Wellbutrin for example is a strong DA reuptake inhibitor and only works on NE half so much.
This is also a big find because it is the first time (according to another article) that they have determined the actual mechanism of how a drug works in the brain on a finer level than simply stimulating various receptor sites and seeing what happens.
(if you do a google search, a ton of similar stories come up)
http://www.bio-medic...tworks-20105-1/
