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Phentolamine with stimulants?

If cardiac issues are a problem, reduce your dose or change stimulants. Playing with adrenergic (ant)agonists just has too much potential for harm (rebound hypertension etc)

and by the way, phentolamine has a half life of about 19 minutes and hence should probably be injected. so I don't think it's a real good drug for everyday usage- better for rescue in amphetamine overdose...
 
sekio said:
If cardiac issues are a problem, reduce your dose or change stimulants. Playing with adrenergic (ant)agonists just has too much potential for harm (rebound hypertension etc)

and by the way, phentolamine has a half life of about 19 minutes and hence should probably be injected. so I don't think it's a real good drug for everyday usage- better for rescue in amphetamine overdose...
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Perhaps something like Phenoxybenzamine is more appropriate given the 24 hour half life?

Intermittent adrenergic blocker use shouldn't cause anywhere near the hypertension of the underlying stimulants. I've done caffeine+propranolol before, and never had the slightest in rebound hypertension.

The entire idea is to remove side effects from stimulants, and there is at least some evidence in medical literature of using adrenergic antagonists as an adjuvant to stimulants with good results: http://journals.lww.com/jonmd/Abstr...on_of_Treatments_for_Attention_Deficit.9.aspx

What agent is appropriate really varies from stimulant to stimulant. In general I'd lean towards alpha blockers for amphetamines.
 
tweex said:
Perhaps something like Phenoxybenzamine is more appropriate given the 24 hour half life?

Intermittent adrenergic blocker use shouldn't cause anywhere near the hypertension of the underlying stimulants. I've done caffeine+propranolol before, and never had the slightest in rebound hypertension.

The entire idea is to remove side effects from stimulants, and there is at least some evidence in medical literature of using adrenergic antagonists as an adjuvant to stimulants with good results: http://journals.lww.com/jonmd/Abstr...on_of_Treatments_for_Attention_Deficit.9.aspx

What agent is appropriate really varies from stimulant to stimulant. In general I'd lean towards alpha blockers for amphetamines.
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Propranolol =/= alpha blocker

Propranolol is a beta selective blocker and doesn't share the risk of rebound hypertension with alpha blockers. I think sekio's concern is that you would take an alpha blocker for an extended period of time, then stop abruptly. That schedule could be dangerous. What do you think the benefit would be?
 
endotropic said:
Propranolol =/= alpha blocker

Propranolol is a beta selective blocker and doesn't share the risk of rebound hypertension with alpha blockers. I think sekio's concern is that you would take an alpha blocker for an extended period of time, then stop abruptly. That schedule could be dangerous. What do you think the benefit would be?
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Well yes, of course! Some stimulants work better with alpha blockers (amphetamine as an example), and other with beta blockers (methylphenidate as an example). I've mostly done the combo of propranolol and caffeine, and it really works wonders. The entire idea is to decrease/eliminate (negative) cardiovascular effects of the stimulant without interfering with central nervous system activity...
 
Beta blockers can be dangerous with stimulants, due to a paradoxical vasoconstrictive effect, caused by all the pressor amines that would have bound beta receptors having nowhere else to go, and binding instead, alpha adrenoreceptors.

Clonidine is, I find, the best with stimulants, or other alpha2 adrenoreceptor agonists. Apha2 is the adrenergic autoreceptor, which means, when stimulated by an agonist, it tells the brain too much (nor)adrenaline is in play, and thus applies the brakes. It is, unlike beta blockers, also effective against anxiety, is sedating and calming. I love the stuff personally, although I am not at all a big stimulant fan. (for instance, 3 small puffs on a very stingily loaded pipe of methiopropamine earlier today, when I got the rare desire for a stimulant, was quite enough for me, with another tiny one later, without reloading the pipe. Might just have another tiny little hit again, but thats quite enough for my tastes)
 
Limpet_Chicken said:
Beta blockers can be dangerous with stimulants, due to a paradoxical vasoconstrictive effect, caused by all the pressor amines that would have bound beta receptors having nowhere else to go, and binding instead, alpha adrenoreceptors.

Clonidine is, I find, the best with stimulants, or other alpha2 adrenoreceptor agonists. Apha2 is the adrenergic autoreceptor, which means, when stimulated by an agonist, it tells the brain too much (nor)adrenaline is in play, and thus applies the brakes. It is, unlike beta blockers, also effective against anxiety, is sedating and calming. I love the stuff personally, although I am not at all a big stimulant fan. (for instance, 3 small puffs on a very stingily loaded pipe of methiopropamine earlier today, when I got the rare desire for a stimulant, was quite enough for me, with another tiny one later, without reloading the pipe. Might just have another tiny little hit again, but thats quite enough for my tastes)
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Interesting to hear Clonidine works well. And apparently the theoretical harm from beta-blockers with some stimulants isn't as clear cut in practice: http://www.sciencedirect.com/science/article/pii/009130579090071O
 
tweex said:
Interesting to hear Clonidine works well. And apparently the theoretical harm from beta-blockers with some stimulants isn't as clear cut in practice: http://www.sciencedirect.com/science/article/pii/009130579090071O
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That study you cited suggests that propranolol protects against stimulant induced seizure activity, it doesn't tell you anything about cardiovascular toxicity. Considering how resilient rodents are to cardiovascular insults I wouldn't look for a mouse study to answer that question.

The problem with stimulant + beta-blocker is the unopposed a1 agonism. Why not look at a combined beta/a1-blocker a la Labetalol?
 
Well its hardly surprising. Amphetamines and the like typically release (and with some stimulants, inhibit reuptake of) noradrenaline as well as DA (and sometimes, as with meth, 5HT also), clonidine and similar drugs act to reduce noradrenaline release.

I find its the best thing (strong opiates aside..although I generally only do stimulants when I have both) to come down with, it really kills the jitteryness too, and the sedating effect helps aid relaxation or sleep after. Does have a very pronounced hypotensive effect though.
 
endotropic said:
That study you cited suggests that propranolol protects against stimulant induced seizure activity, it doesn't tell you anything about cardiovascular toxicity. Considering how resilient rodents are to cardiovascular insults I wouldn't look for a mouse study to answer that question.

The problem with stimulant + beta-blocker is the unopposed a1 agonism. Why not look at a combined beta/a1-blocker a la Labetalol?
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Yes, does look like overall a better drug for more powerful stimulants. With caffeine, propranolol doesn't seem to cause unopposed alpha a1 agonism in any reasonable dose, but this could indeed be a problem with much more powerful stims. Even nicotine doesn't play well with beta blockers alone apparently: http://ebm.sagepub.com/content/123/1/174.short

Limpet_Chicken said:
Well its hardly surprising. Amphetamines and the like typically release (and with some stimulants, inhibit reuptake of) noradrenaline as well as DA (and sometimes, as with meth, 5HT also), clonidine and similar drugs act to reduce noradrenaline release.

I find its the best thing (strong opiates aside..although I generally only do stimulants when I have both) to come down with, it really kills the jitteryness too, and the sedating effect helps aid relaxation or sleep after. Does have a very pronounced hypotensive effect though.
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I will definitely give clonidine a try and measure my heart rate/bp while resting on various doses of various stimulants to figure out optimal clonidine dosing, and post results... when I get around to it. I'm not much of a downer fan, so I'm primarily looking at keeping the positive effects of stimulants without burning out your cardiovascular system.

Although non-adrenergic stimulants like Modafinil and Phenylpiracetam really are awesome (albeit non-recreational) in their own right.
 
Well caffeine isn't really typical at all. And to get to the kind of territory where you needed alpha blockers for vasoconstriction...I'd think one's head would explode first from the excessive stimulant effect =D

What is phenylpiracetam like? I really want to try it myself.

And the mechanism of action of alpha2 agonists, its just activating the autoreceptor, tricking the brain into thinking theres too much noradrenaline around, so it stamps on the breaks and shuts it down. Great for cracked out , strung out comedowns.
 
Limpet_Chicken said:
Well caffeine isn't really typical at all. And to get to the kind of territory where you needed alpha blockers for vasoconstriction...I'd think one's head would explode first from the excessive stimulant effect =D

What is phenylpiracetam like? I really want to try it myself.
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I'm interested in totally suppressing cardiac effects of stims, not just preventing imminently dangerous hypertension.

Phenylpiracetam feels fairly similar to d-amphetamine as far as motivating you and keeping you focused and full of energy, but not euphoric. The nice part is it has been totally side effect free for me, the effects wear off after a few hours with no comedown. No induction of anxiety, changes in cardiovascular system, and clear nootropic effects.

Really recommended, and is probably my favorite functional stim atm. Just builds temporary tolerance if used day after day, so you need to cycle it.
 
tweex said:
I'm interested in totally suppressing cardiac effects of stims, not just preventing imminently dangerous hypertension.

Phenylpiracetam feels fairly similar to d-amphetamine as far as motivating you and keeping you focused and full of energy, but not euphoric. The nice part is it has been totally side effect free for me, the effects wear off after a few hours with no comedown. No induction of anxiety, changes in cardiovascular system, and clear nootropic effects.

Really recommended, and is probably my favorite functional stim atm. Just builds temporary tolerance if used day after day, so you need to cycle it.
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https://en.wikipedia.org/wiki/Intuniv

Guanfacine is very similar to clonidine with a way longer half life. Clonidine is about 4 hours tops... I would recommend guanfacine over clonidine , at least from looking at the pharmacology of it...
 
Phentolamine is an antagonist at both Alpha 1 and Alpha 2 receptors. It is a competitive antagonist with a 4 hour duration effect.Though it induces reflex tachycardia it blocks the presnyaptic alpha 2 receptors in proximity to the heart. This intself causes reflex tachycardia a high heart rate . Though it also lowers blood pressure by blocking Alpha 1 receptors in periphery. Where as noradrenaline is an alpha 1 agonist and causes peripheral vasoconstriction. Phentolamine and Phenoxybenzamine are less effective in lower blood pressure than the Alpha 1 selective blockers which have less reflex tachycardia. IF your on Amphetamines or Cocaine would you want that tachycardia to get worse? I would recommend Clonidine if anything.
Though im not sure. I just know the Phentolamine and phenoxybenzamine induce tachycardia.
 
Turns out clonidine has more affinity for alpha 2 receptors than Phenoxybenzamine or Phentolamine. Mixing the two should result in clonidine winning out on the alpha 2 receptors, and phenoxybenzamine/phentolamine behaving like a selective alpha 1 blocker.
 
limpet chicken said:
Amphetamines and the like typically release (and with some stimulants, inhibit reuptake of) noradrenaline as well as DA
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In fact, no known non-norepinephrinergic DA releasers exist. I don't recall whether there are even any that are even selective for DA over NE...maybe 4fa (but you get some 5ht action on the side). Even king meth exerts its greatest action at DAT.
...
I've heard from a few people who are hyper-responsive to adrenergic activation that concurrent clonidine is a 'good scene'.

ebola
 
These aren't technically Alpha "Blockers" perse. Alpha "blockers" actually bind to and agonize the alpha 2a adrenergic receptor. A2a is actually an autoreceptor. This means it monitors levels of neurotransmitters (in this case Norepinephrine). When a substance binds to and agonizes it, this fools the receptor into believing that levels of that neurotransmitter are too high, so it induces reuptake.

Also...

You seem to mention Selegiline a ton in nearly all of your posts. I'm sure you already know just how dangerous mixing Monoamine Oxidase Inhibitors with stimulants is. However, you're scaring me. I remember hearing you mention taking Meth with Selegiline a day or so ago. Now 800MG's of Caffeine?! I know you know this, you know you know this, I shouldn't have to say this......STOP!

It doesn't matter how low of a dose of Selegiline you're taking. Mixing these stimulants with an MAOI IS SLOWLY KILLING YOU! Even if you don't feel anything bad happening, there is tons of horrible things that are taking place in your CNS because of this combination. To name a few, "widespread destruction of synapses, and general promotion of nerve death". I'm not making this up.

Here's the link for the quote - http://www.ncbi.nlm.nih.gov/pubmed/15554766

Eventually, this combination is going to overstimulate your brain so much you will have a seizure.

I beg you, please. Respect harm reduction. Stop combining Selegiline with ANY OTHER DRUGS!
 
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