Coop's Corner #4: Alpha-2 Antagonism? Yes Please.

mr.cooper69

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As many of you may already know, alpha-2-antagonists are simply compounds that antagonize the alpha-2-adrenoreceptor. The most popular ones are yohimbine, rauwolscine, and a variety of yohimbe alkaloids.


These 3 categories of alpha-2-antagonist each possess a unique goal-specific attribute, but before we delve into specifics, let's look at how effective these compounds are for fat loss.


The relevant research on this topic shows that yohimbine is extremely effective for fat loss.


Yohimbine: the effects on body compos... [Res Sports Med. 2006 Oct-Dec] - PubMed - NCBI


The researchers didn't just use anyone. They used lean athletes. How lean? Both groups started at roughly 9% bodyfat. To put that in perspective:





So these guys are shredded. And they're active, so they probably have a good deal of LBM. After 21 days of yohimbine supplementation, placebo remained unchanged but the yohimbine group lost about 2% bodyfat, taking them all the way to 7% BF. No significant changes in muscle mass or performance were noted.


So:

3 weeks of Yohimbine supplementation caused a 2% reduction in bodyfat from an already shredded baseline of 9% BF, all the while preserving muscle mass and strength/endurance.



To put this in perspective, again refer to the bodyfat chart. These athletes went from the far right image to the middle image in 3 weeks, without major changes to diet or exercise regimens. That's extremely impressive.






So which form of yohimbine is best? That'll depend on your goals.


Yohimbine possess extreme affinity for the alpha-2-adrenoreceptor, but due to receptor homology with various 5-HT receptors, yohimbine HCl is highly anxiogenic and is clinically used to model panic disorder. The effective dose is 0.2mg/kg in isolation. If you combine any of these alpha 2 antagonists with caffeine or beta-agonists (aka synergists), the necessary dose decreases quite a bit.


Rauwolscine lacks significant activity at the 5HT receptors, but it has its own issues. It's less potent than yohimbine, requiring a markedly higher dose to elicit the same effects. Furthermore, it's partially adrenolytic, as it is less selective than yohimbine on the adrenergic system, partially antagonizing alpha-1- adrenoreceptors.


And then we have the various yohimbe alkaloids like 11-OH yohimbine, that are alpha-2-antagonists (not to be confused with a broad-spectrum extract of alkaloids). These compounds act similarly to yohimbine for fat loss but seem to promote a feel-good energy as well. They also have significantly longer half-lives than either yohimbine or rauwolscine, making them a great choice earlier in the day.


So which one works best? It's goal-specific. The most effective for fat loss will be yohimbine or yohimbe alkaloids. The most effective for someone prone to anxiety will be rauwolscine or yohimbe alkaloids (if you have anxiety disorder, you should not be using any of these).


What works best with alpha-2-antagonists? Well here's a brief physiology lesson. The alpha-2 receptor is an autoreceptor, meaning it is located NOT on the postsynaptic neuron chiefly, but on the pre-synaptic neuron. It acts to PREVENT further release of fat burning catecholamines: this is why we want to antagonize (inhibit) it. It's thought that stubborn fat is particularly rich in these alpha-2-receptors, hence why fat loss is always inhibited in these regions. For those seeking to lose stubborn fat, alpha-2-antagonists are a great option.


Alpha-2 antagonists synergize with anything that potentiates catecholamine release. This means caffeine, exercise, forskolin, and beta-agonists all work exceptionally well with alpha-2 antagonists. Furthermore, because alpha-2 antagonism can increase insulin release, these compounds are best taken fasted. A fasted state promotes the counter-regulatory cascade anyway (increased NE/E), so it's the perfect time to dose these, along with preworkout dosing.








So, in summary:


1. Yohimbine or Yohimbe alkaloids are the preferred choice for fat loss; rauwolscine or yohimbe alkaloids may be preferred if one is prone to anxiety.
2. The recommended dose for yohimbine is 0.2mg/kg BW in isolation. If you take it with synergists, the dose needed is less. Rauwolscine needs a higher dose.
3. These compounds have been found to be extremely effective for fat loss, even if you're already very lean and borderline-contest ready. There is also a considerable body of data showing they help with erections. If there's one supplement to consume orally for stubborn fat loss, it's an alpha 2 antagonist.
4. These compounds synergize with caffeine, exercise, forskolin, or beta-agonists. They should be dosed in a fasted state or prior to exercise for maximum results.
5. Recommended products:


a. PES Alphamine
B. iForce Dexaprine XR
c. ECY (use extreme caution)
d. PES Alpha-T2
e. OxyElite Pro with Purple Top
f. PES Enhanced
g. Muscletech Hydroxystim
h. Athletix Acute FX


*Yohimbine should be avoided in concert with Tyrosine or in those diagnosed with anxiety disorder.
 
Driven2lift

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Love the simplified, to the point layout on the latest corner's Coop, easy to read through and understand without re-reading as I sometimes have to lol.

Yohimbe has been great for me in the past and luckily I have yet to get stopped by customs so I will keep pushing my luck
 

cbsharpe

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Hmmmm...I wondering if I should add a stand alone Yohimbe/Yohimbine product to my arsenal....
 
Pride89

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Perfect, thank you !

Only one prob with Yohimbe for me, i get crazy cravings ?
 

davidmma

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Thanks for the article mr coop. I always enjoy reading up on your stuff very informative. I think I will be adding one of these to my stack.
 

pectus

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just a question mr.COOPER.

can you explain better this??
" Yohimbine possess extreme affinity for the alpha-2-adrenoreceptor, but due to receptor homology with various 5-HT receptors, yohimbine HCl is highly anxiogenic and is clinically used to model panic disorder. "

This means it is PRO serotonine or against serotonine ?
 

mr.cooper69

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Neither. It means certain serotonin receptors get blocked, so the serotonin that would otherwise agonize those receptors shifts to other receptor subtypes. It modulates serotonin signaling, rather than being pro or anti
 
LizKing531

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Perfect, thank you !

Only one prob with Yohimbe for me, i get crazy cravings ?
Yeah me too - seriously hungry shortly after taking
 

uubiduu

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If i remember the advertising of the og oxyelite pro by usp labs,they tried to explain why alpha-yohimbine was better than yohimbine-hcl.After having read that ad in the past i was really thinking that the y-hcl was worthless for fatloss.any ideas?
 

mr.cooper69

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If i remember the advertising of the og oxyelite pro by usp labs,they tried to explain why alpha-yohimbine was better than yohimbine-hcl.After having read that ad in the past i was really thinking that the y-hcl was worthless for fatloss.any ideas?
Did you read the thread? I thought it was laid out pretty neatly. Yohimbine HCl is more potent, but alpha-yohimbine is preferred if you can't tolerate yohimbine hcl due to side effects
 
Pride89

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Yeah me too - seriously hungry shortly after taking
Have you build some kind of tolerence towards this ? I've been increasing dose very slowly for 1 month now and Its better now but still, im taking it to Cut some fat and not eat sweets all the time !?
 

chedapalooza

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I take 1000mg tyrosine split into two 500mg doses. How far apart should I dose it from YC stack?

Should the Y be taken all In one daily dose or split over the course of your fasted state? (Using 2.5mg caps) goal dose is 15mg
 

mr.cooper69

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I take 1000mg tyrosine split into two 500mg doses. How far apart should I dose it from YC stack?

Should the Y be taken all In one daily dose or split over the course of your fasted state? (Using 2.5mg caps) goal dose is 15mg
That dose is pretty low to begin with for tyrosine. How you split the yohimbine dose doesn't matter a whole lot. Preworkout > fasted > feeding
 
LizKing531

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Have you build some kind of tolerence towards this ? I've been increasing dose very slowly for 1 month now and Its better now but still, im taking it to Cut some fat and not eat sweets all the time !?
I haven't taken it very long solo, so no real tolerance to it either. Mostly I've had it in fat-burner supps & never really had any appetite increase issues. Just figured I might as well reframe my thinking on sweets, sorta like quitting smoking...
 

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Great thread...Coop,

Why does Yohimbine cause congestion and is there anything that can be done about it?

I get horrible congestion from HCL and Alphaburn, but Im completely fine with Alphamine.
 

mr.cooper69

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Great thread...Coop,

Why does Yohimbine cause congestion and is there anything that can be done about it?

I get horrible congestion from HCL and Alphaburn, but Im completely fine with Alphamine.
It can, and there's not much you can do besides lowering the dose
 
ryanp81

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Coop your articles are awesome and I love alpha t-2 but once in awhile when I take it or when I take a break from it and get back on it the first couple of doses I get really agitated and just pissed off...It's hard to explain, I'm figuring its the Y.
 

mr.cooper69

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Coop your articles are awesome and I love alpha t-2 but once in awhile when I take it or when I take a break from it and get back on it the first couple of doses I get really agitated and just pissed off...It's hard to explain, I'm figuring its the Y.
This is actually an effect seen with any stim generally. It's funny that steronz take so much heat for "rage," when a much more common mechanism is increased norepinephrine levels which make you snap early. But as you said, after a few uses you get acclimated to it
 

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So hypothetically, in a none officially recommended way... yohimbine+albuterol would make a great stack before the summer? is there a point of diminishing returns or any extra cause for concern when using multiple alpha+beta antagonist? such as adding forskolin-95 to mentioned stack..
 

mr.cooper69

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So hypothetically, in a none officially recommended way... yohimbine+albuterol would make a great stack before the summer? is there a point of diminishing returns or any extra cause for concern when using multiple alpha+beta antagonist? such as adding forskolin-95 to mentioned stack..
Albuterol is a b-agonist
Yohimbine is an alpha-2 antagonist
Forskolin is a cAMP elevator that potentiates both pathways

All 3 are synergistic. This also means that if one were to hypothetically use all 3, they'd need lower doses of each or side effects may arise
 

squirtguns89

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cool. thanks for doing these coopscorners too, ive read them all. great condensed reading material for those of us who struggle with interpreting information at times. hope you keep putting them out.
 
bigdavid

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Albuterol is a b-agonist
Yohimbine is an alpha-2 antagonist
Forskolin is a cAMP elevator that potentiates both pathways

All 3 are synergistic. This also means that if one were to hypothetically use all 3, they'd need lower doses of each or side effects may arise
Some antipsychotics and antidepressants have some moderate-strong alpha-2 antagonism. Mirtazapine comes to mind. Would they also be effective for fat loss? (assuming you could deal with the increased appetite and somnolence from the blocking 5HT-2C and H1)
 

mr.cooper69

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Some antipsychotics and antidepressants have some moderate-strong alpha-2 antagonism. Mirtazapine comes to mind. Would they also be effective for fat loss? (assuming you could deal with the increased appetite and somnolence from the blocking 5HT-2C and H1)
They would not. And there are veeeery few alpha-2-antagonists on the drug market, with the only really common one being what you mentioned: mirtazapine. However, mirtazapine has a lot of mixed activity, not just at the serotonin receptor, but at other sites as well. This prevents us from reaching a therapeutic dose for fat loss in the periphery.

Conversely, yohimbine is exceptionally selective for the alpha 2 receptor.

You raise an interesting point though with respect to the other side of the coin: alpha 2 agonism. Clonidine is a BP med that has recently come into the spotlight for its ability to reduce pain. Which is interesting, because agmatine, another alpha 2 agonist, has been found to reduce pain in humans as per studies and reduce BP as well as per BF cuff tests. I see a bright future for agmatine in the medical realm
 
bigdavid

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They would not. And there are veeeery few alpha-2-antagonists on the drug market, with the only really common one being what you mentioned: mirtazapine. However, mirtazapine has a lot of mixed activity, not just at the serotonin receptor, but at other sites as well. This prevents us from reaching a therapeutic dose for fat loss in the periphery. Conversely, yohimbine is exceptionally selective for the alpha 2 receptor. You raise an interesting point though with respect to the other side of the coin: alpha 2 agonism. Clonidine is a BP med that has recently come into the spotlight for its ability to reduce pain. Which is interesting, because agmatine, another alpha 2 agonist, has been found to reduce pain in humans as per studies and reduce BP as well as per BF cuff tests. I see a bright future for agmatine in the medical realm
Whenever I take agmatine I feel like I can't think as clearly. It is rather annoying, especially when I'm trying to learn something. I'm assuming it's from the NMDA antagonism.
 

mr.cooper69

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Whenever I take agmatine I feel like I can't think as clearly. It is rather annoying, especially when I'm trying to learn something. I'm assuming it's from the NMDA antagonism.
It's unlikely. NMDA antagonism would prevent excitotoxicity at low concentrations (aka relevant agmatine concentrations) and block long term potentiation at higher concentrations (likely need to be injected). The latter would disrupt memory formation, not thought clarity which is more of a prefrontal, cholinergic phenomenon
 
bigdavid

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It's unlikely. NMDA antagonism would prevent excitotoxicity at low concentrations (aka relevant agmatine concentrations) and block long term potentiation at higher concentrations (likely need to be injected). The latter would disrupt memory formation, not thought clarity which is more of a prefrontal, cholinergic phenomenon
Didn't make sense to me either. However, I had the same feeling from magnesium glycinate and magmind so I just assumed that's all it could be.
 

chedapalooza

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Didn't make sense to me either. However, I had the same feeling from magnesium glycinate and magmind so I just assumed that's all it could be.
What did magnesium glycinate do? I was taking it for 2 months and ran out, switched back to mag citrate at bed... I feel since dropping the glycinate that fatigue and mental clarity have become issues
 
bigdavid

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What did magnesium glycinate do? I was taking it for 2 months and ran out, switched back to mag citrate at bed... I feel since dropping the glycinate that fatigue and mental clarity have become issues
With magnesium glycerinate (was taking 400 mg before bed for about a week). After about 3 days I started to feel very mentally foggy and fatigued and that supplement was all that had changed. I felt like I couldn't learn as fast as I usually could and I just felt crappy, basically. After a week on it I stopped and slowly my mind felt better after a few days. Then tried magmind (magnesium l-threonate) and the same thing occurred but this time it was after only 2 days. Similar happened with agmatine but it was not as pronounced as the magnesium.
 

dpk33

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That dose is pretty low to begin with for tyrosine. How you split the yohimbine dose doesn't matter a whole lot. Preworkout > fasted > feeding
When you say preworkout > fasted > feeding, does that mean the fat burning effects will be there if you take it preworkout even if you aren't fasted (2 hours after eating for example)?
 

dpk33

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What should the dose of Y HCl be if taken with caffeine and ephedrine? and how many times per day?
 

chedapalooza

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What should the dose of Y HCl be if taken with caffeine and ephedrine? and how many times per day?
No rep will recommend an ECY stack due to safety issues. I have done this, as have others and done 2 doses of 200mg C, 25mg E, 1.5-3mg Y twice a day. Do NOT do this before HIIT cardio.
 
Synapsin

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No rep will recommend an ECY stack due to safety issues. I have done this, as have others and done 2 doses of 200mg C, 25mg E, 1.5-3mg Y twice a day. Do NOT do this before HIIT cardio.
Sound advice right here.
 

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