Alpha-2A receptors?

Question

Guanfacine ER is a selective agonist, it works at these receptors.

I know they are found throughout the central nervous system.... but what would this drug do?

It's an ADHD drug if that helps. I just don't get how it works. This would increase activity of norepinephrine, right? But why does it matter what kind of receptor? Why alpha-2A?

Any.... any information at all is appreciated.

Answer 1

I am not a specialist concerning the specifics of the alpha-2A

receptor, or ADHD, but I do know a lot of the basics.

Norepinephrine (NE) is one of the most common neurotransmitters in the body (not just the central nervous system), along with a neurotransmitter called acytelcholine . Together these two neurotransmitters control everything from heart rate to synaptic firing to breathing - you name it. It is very common for there to be different classes of the same neurotransmitter receptor. These different classes of neurotransmitter receptors allow for specificity in the bodily responses to a neurotransmitter, and can vary in concentration from one part of the body to another. These different classes have very small changes in protein folding and structure, and a different impact on the body. Different drugs target different classes of neurotransmitter receptors, causing different reactions in the body.

In pharmacological issues, it is important to minimize side effects, so it is common to target one class of receptor to maximize the drug's positive effect, and minimize any bad side effects.  Other NE receptor classes in the brain may be able to work on ADHD symptoms, but they may have more severe side effects.

The fact that the drug is a selective agonist means that, yes, it selectively works at the alpha-2A NE receptors only. This works well, since the drug will then primarily work on the brain, and not in other regions of the body. Specifically in the brain, it will work on the prefrontal cortex and hippocampus, allowing for better concentration. The neurotransmitter will undergo the process of re-uptake into these neurotransmitter receptors on the synapse of the neuron, which can  then perform the release of other neurotransmitters. Neurotransmitters tend to "pool" around the receptors that they work on, and the drug may not be increasing the activity of NE. It may be allowing for a more steady use of NE, or another neurotransmitter, instead of a big burst of use, which would result in the depletion of the NE pool around the neurotransmitter.

Just in case this sounds a bit confusing: The neuron can receive in and send out chemical signals (neurotransmitters) through foot-like appendages called synapses.These synapses contain many neurotransmitter receptors. An easy way to think of these receptors is to think of them like pores. They can be active and open (such as with an agonist), or they can be clogged and inactive (such as with an antagonist).

Answer 2

The type of receptor matters because neurotransmitters and hormones are specific to their receptors.  The drug may bind the receptor and mimic the effects of norepinephrine binding.  Apparently norepinephrine activity has some effect on ADHD symtoms and mimicking norepinephrine's activity by taking this drug decreases ADHD symptoms.  If the drug acted at a different receptor it would mimic the effects of a different neurotransmitter and would not have the same results.