I thought part of ADHD was a deficiency in Norepinephrine(dopamine too), and clonidine is an a2 agonist which LOWERS norepinephrine in the brain.

Stratters on the other hand INCREASES NE levels.

I can't edit posts, so I'll add this here: I'm not talking about clonidine in addition to a stimulant, but clonidine by itself is also sometimes used for ADHD.

I don't think clonidine really works like that . It enhances the firing or binding of NE in the feedback loop in the pre frontal cortex. I am not totally certain on how exactly it works but it is supposed to enhance working memory. Some studies support this while other studies report no changes in adult males and that sedation was a problem. I have found that it does help calm the mind by eliminating distractions and thus enhances attention to a target stimulus. Anyways, adhd really does suck.

Your correct that alpha-2 stimulation reduces NE levels which leads to lower alpha-2 stimulation from NE. While this could make dosing more difficult it seems like alpha-2 medications are useful in treating adhd.

It has been established that ADHD responds best to a mix of Dopamine + NE stimulation. vs only dopamine stimulation or only NE stimulation.

So its more of a question of how much adhd symptom improvement from the NE side comes from NE overall vs NE stimulation of alpha-2 receptors.

I wonder if a med combo which hits dopamine + alpha 2 receptors would work as well as stims + have less side effects from increasing NE levels.

Bobc

I theorize that focalin or ritalin plus wellbutrin with an alpha agonist would work

Clonidine... in theory, acts as an alpha agonist that works through feed back inhibition and regulates sympathetic outflow. (Read this to understand the role of the sympathetic nervous system in general http://www.sciencedaily.com/articles/s/sympathetic_nervous_system.htm(

It essentially inhibits the fight or flight response from taking control on the pfc regions and there by preventing a cause of impulsivity or hyperactivity. It allows you to have more control over you basically.

Hyperactivity in adults looks like stress, anxiety, worry etc. The main issue with adhd is that our fight or flight responses are always primed. That's what the general research shows anyways. Hyperactivity is a complex thing really, in that it can look like anxiety, express itself as anxiety but not actually be anxiety. For example, general anxiety is too much dopamine in the brain which competitively inhibits a lot of the serotonin in ones brain. These are your GAD and OCD disorders that can look very similar to adhd sometimes. The difference is that ADHD is caused (in theory) by a lack of DAT transporter and several other chemical messengers. So you wouldn't approach ADHD treatment by lowering dopamine rather, you'd essentially target the source of anxiety (the sympathetic systems) and block it's affect on the rest of the cns and pfc systems so that one could take a stimulant without getting fight or flight reactions all the time or just be calm without stimulant medication in general, if they are primarily hyperactive.

That's just my general understanding, I apologize if i'm wrong and by all means take what I say with a grain of salt. Feel free to correct me if im wrong

This is copied from a course I recently took.


It´s a partial agonist of Norepinephrine, it decreases tonic and phasic activity of the locus ceruleus making it a little less erratic. There's also evidence that it increase the efficiency of neurotransmission in the prefrontal cortex. This med helps people who are highly aroused, impulsive, emotionally charged up, irritable, explosive. They also help to reduce anxiety, defiance and agression and they're useful for controlling tics.

They work primarily at the norepinephrine neuron. Clonidine works at Alpha 2A, 2B and 2C receptors, What happens is that the medications stimulate the Alpha 2A receptors, which increases cyclic AMP production, which closes the nearby HCN channels, and increases then, the dendritic cell excitability. And it strengthens the connectivity of the microcircuits of the dorsal lateral prefrontal cortex. So in working memory and distractibility in monkeys and in humans, is improved. Distractibility is reduced. And the profusion during working memory tasks in these areas is enhanced in monkeys, when you give them either Guanfacine or Clonidine.

The right amount of norepinephrine stimulation then causes the Alpha 2A receptors to inhibit cyclic AMP and therefore the neurons communicate more effectively. In this slide here, you can see this is a taken from a cross section of the den, the prefrontal cortex, dendritic spines. Under optimal neurotransmission Guanfacine or norepinephrine work at reducing cyclic AMP, and therefore the, the there's less of a, of a decline in the, in the signal. Whereas without alpha 2A stimulation, cyclic AMP allows the signal to be diverted away. And that's suboptimal transmission.

So, when there's inadequate stimulation then the, the ion channels are, are open, and that weakens the neuronal input and so this is where the indirect effect, if you will, of the adrenergic receptors plays a role in, in neurotransmission in the prefrontal cortex. Presumably, then, that will increase both concentration and task completion and efficiency

. Side effects, though, of the Alpha 2A Adrenergic agonists are important to consider. There's sedation and fatigue, and dizziness and these could be rate limiting problems. If you have to dose these medications very gradually in order to avoid the problems of sedation, fatigue and dizziness. There can also be side effects such as dry mouth, indigestion and nausea. Occasionally it slows the heart rate down and lowers the blood pressure, because after all, that's what these medications were designed for. There can also be nightmares and insomnia. Anxiety can be seen, depression. Rarely hallucinations. And if you suddenly stop these medications, the blood pressure can go up and become hypertension. So again, these medications can be very effective, but the side effects need to be managed very, very closely. And again, this is another important feature of these agents, that they improve neurotransmission throughout the day, and can also have beneficial effects on things like aggression and tics.

I´m sure you will understand it far better than me.