Alpha 2 Agonists Puns

Hello!

To sum up my situation, I got bad bad anxiety and have been tested to have an attention deficit and hyperactivity but not ADHD. I was put on mirtazapine which is helping a lot for depression (been in remission for three months!). Later in my treatment, the shrink put me on guanfacine, an alpha-2 agonist. That stuff nuked my anxiety and let me do things I never thought I could do before, but it gave me some side effects that made me stop taking the medication. My psych subsequently put me on Wellbutrin, which helped my class performance, but also made my anxiety shoot through the roof.

Now, I am on the hunt for something that is similar to guanfacine in its MOA, as an alpha-2 agonist. Since guanfacine worked so well for me and Wellbutrin dramatically increased my anxiety, I think my anxiety could possibly be controlled by a decrease in norepinephrine release. I am not sure what supplement works in this way. Do any of you all know?

Just for reference my stack is: mirtazapine 30mg, buspirone 10mg 3x day, propranolol 20mg as needed, lutein, Vit.D/K (deficient), phosphatidylserine, magnesium glycinate, melatonin and zinc.

which one is the best and why?

View Poll

I know stimulants usually mess with dopamine but i guess noradrenergic is also a stimulant

I was wondering if there were any alpha-2 agonists found in herbs or OTC nootropics? Clonidine is used in the treatment of hypertension, anxiety... and ADHD. As is Guanfacine, but that has preference for α2A, which is probably so selective it would be impossible to find in herbal form/source.

(I'm 99% sure I have ADHD, which means I should get back on low-dose caffeine, but it gives me anxiety.)

I am curious as I read a lot about the dangers of abrupt discontinuation of beta blockers, but never that much about alpha agonist (e.g clonidine) or alpha blocker (prazosin) withdrawals.

From what I understood, agonism of beta receptors has a direct effect on cardiac output, but not much on vasodilation and vasoconstriction. Yet alpha agonists target the body’s autoreceptors that are triggered in case of excessive catecholamines. I also read that beta and alpha receptors each respond to adrenaline or noradrenaline (specific to each receptor type).

Which class of drugs, in theory, would be more dangerous to stop abruptly? And why?

If these drugs reduce sympathetic outflow from the CNS, how would ED occur as a potential side effect? Would this occur solely from decreased blood pressure?

Alpha 2 is a Gi receptor. So if it's activated adenylate cyclase will be inhibited and we will have reduced cAMP. But cAMP in vascular smooth muscle inhibits MLC Kinase, resulting in vasodilation and reduced BP. Isn't reduced cAMP supposed to stimulate MLC Kinase, resulting in vasoconstriction and an increase in BP?

Are you currently or have you taken an alpha agonist (AA) (I.e. Clonidine or guanfacine) as an adjuvant therapy (along with a stimulant) to mitigate the strong emotional dysregulation associated with RSD? And does/did it work? What was it like?

I recently started listening to podcasts with Dr. William Dodson (a psychiatrist who specializes in ADHD in adults and children) after he was recommended by a fellow Redditor as a good source. Dodson indicates that 60% of people with ADHD related RJS experience great relief of their RJS emotional dysregulation when one of these alpha agonists is used alongside a stimulant. I’m curious to hear about your experience if your familiar with this line of treatment. Tia!

Following up on a post from a while back where someone combined the alpha-2 adrenergic agonist tizanidine with RC dissos, I thought I'd share my experiences combining clonidine (also an α2 agonist) with 3-HO-PCP and O-PCE.

There isn't really much to add unless you haven't seen the previous post I'm referencing:

Basically clonidine seems to behave a lot like tizanidine in terms of it reducing the peripheral vasoconstriction and general stimulation that some of the more stimulating dissos (e.g. 3-MeO-PCP, 3-MeO-PCE, O-PCE, and 3-HO-PCP) can cause.

Taking 75μg of clonidine prior to vaping O-PCE resulted in a much warmer and calmer experience, particularly reducing the somewhat uncomfortably stimulating offset that vaped O-PCE has. The same thing goes for insufflated dosages of 3-HO-PCP (which in itself I find to be "warmer" than O-PCE, but still sometimes too stimulating).

I don't intend to encourage anyone to do the same. I just wanted to share my experience. At the end of the day we're still dealing with chemicals that hardly any or no research has been done on.

Hello,

I have been looking online, but have failed to turn this up: Does anyone know of a natural alternative to Clonidine? I am specifically looking for a natural Alpha-2 Receptor Agonist... however I haven't been able to turn anything up. If you have heard of one, can you please post a link to a page referencing or detailing it's pharmacokinetics?

In case anyone is wondering, I am interested in such a supplement/compound specifically as a trial to lessen the withdrawal symptoms of buprenorphine discontinuation. I had used Clonidine before with some success, and would like to find a natural alternative.

Thanks in advance!

Anyone have an personal experience with Alpha-2-Agonists such as Clonidine, Methyldopa, etc? I'm considering getting on this drug to help my POTS. (My doctors believe I have H-Pots) Just wanted to get some information from people who currently take it or have taken it in the past.

How long did you take the drug?

Did/Do you have any side effects?

What is your dosage and did you grow any type of resistance to the treatment?

Can you exercise on this medication?

Here's some further reading, if you're interested: 10.1177/154405910508400703

Am I overlooking something? Stimulants (both amp and methylphenidate) cause me panic and anxiety, even at sub-therapeutic doses. Wellbutrin is energizing but that’s about it. And Intuniv has been very helpful for behavioral and emotional regulation, but attention, focus, and memory aren’t hugely affected. Strattera is really my last resort as the only med I haven’t tried and I’ve heard nothing but negative reviews. Haven’t felt this “stuck” in a while.

α-adrenergic agonists cause K+ to shift out of cells, causing hyperkalemia

But beta-adrenergic agonists cause K+ to shift into cells causing hypokalemia?

How come?

These are novel with very few documented studies, and even fewer on humans. There have been no negative effects documented, and overall it seems to be a more promising wakefulness medication than current stimulant based ones such as Modafil. This is mostly due to the lack of side effects, less addictive (possibly nonaddictive) and lack of tolerance building qualities associated with pure orexin A. Interestingly, the substance also seems to have little or no effect on subjects that are not sleep deprived, while they sustain a natural reservoir Orexin A. It’s also extremely potent, active between 50-200ug, and is said to relieve tiredness by replenishing orexin A once it’s depleted (causing the tired feeling), meaning no jitters.

It’s very possible that the lack of research is to blame for the ‘seemingly’ safe qualities of this nootropic. Honestly though, I’ve read enough to be comfortable signing myself up as a short term Guinea pig, at least while term finals are around the corner. I’d love to read some personal documents though, if any exist. I’ve read only 1 forum where someone reported having purchased the nootropic in 2017. Follow up posts indicated they were excited to purchase again, but no actual report from the person.

For the last year and a half, I have been on a ketogenic diet. Admittedly, it was heavy on saturated fat from dairy. Recently discovered that I have hypofunctioning PPAR-alpha gene. Which now makes perfect sense because I could never get my ketones above 1 mmol (even with a 24 hr fast), and my LDL skyrocketed (~190 on NMR, 86 when not in ketosis). Obviously, there were negatives to that dietary approach for me, but there were also a lot of positives. Not to mention, I would like to take advantage of the potential for longevity, decreasing cancer risk, etc that the ketogenic diet and fasting hold. Since learning this info (on top of the not so stellar labs), I have transitioned to a more Mediterranean diet with an emphasis on PUFAs and MUFAs. I’ve thought about doing periods of ketosis and fasting every now and then, while using PPAR-alpha agonists (like sesamin) to offset the genetic hypofunctioning. Would really like to hear from anyone who has tried this or can give some insight (especially anyone who was checking ketone measurements while doing it).

We know the genocides and invasions of countries, but what smaller things have they done?

I know most stimulants mess with dopamine but i guess noradrenergic is also a stimulant

I know stimulants usually mess with dopamine but i guess noradrenergic is also a stimulant

If these drugs reduce sympathetic outflow from the CNS, how would erectile dysfunction occur as a side effect?