Phenethylamines and alpha/beta receptor affinity

[Cyanoide]

I replied to a few members in the psychedelic sub forum when they asked if it's safe to take beta blockers with phens. My answer was an emphatical no.

Substituted phenethylamines have a more or less high affinity for both alpha and beta receptors. If one would take a beta blocker on top of this, what may follow could be what I call an "unopposed beta blockade", meaning that only beta receptors are blocked but alpha receptors are not. The same thing applies to stimulants like methamphetamine. A possibly dangerous imbalance could follow, as alpha receptors are left unblocked but beta receptors are blocked; at the same time the PEA is firing both at alpha and beta receptors. The result could be a dangerous increase in heart rate and blood pressure.

This is certainly true of "classic" stimulants. However, how right am I in claiming that this also applies to substituted phenethylamines, like e.g. the 2C-X family? 2C-X's are known to have a high affinity for both alpha and beta receptors.

 

[JackiesBabyy]

I think most of the 2c-x family are just 5-HT2a agonists, but I don't know how these interact with beta blockers.

 

[Cyanoide]

I think most of the 2c-x family are just 5-HT2a agonists, but I don't know how these interact with beta blockers.

This is correct, but doesn't answer my question. Psychedelic tryptamines are 5-HT2a agonists too, however almost none of them could cause a dangerous interaction with beta blockers (maybe apart from AMT and 5-MeO-AMT) due to an almost complete absence of noradrenergic activity.

 

[thebac0n]

The effect you are describing sounds like it would happen at massive doses of amphetamine and beta-blocker.

My friends and I actually take low dose propranolol (10-20mg) on our meth binges and it stops the shakes and palpitations quite well.

 

[Cyanoide]

The effect you are describing sounds like it would happen at massive doses of amphetamine and beta-blocker.

My friends and I actually take low dose propranolol (10-20mg) on our meth binges and it stops the shakes and palpitations quite well.

I've once taken 40 mg propranolol on an Ethylphenidate comedown. The effect I got was the complete opposite I had hoped for. I got extreme hypertension which was extremely scary.

 

[JackiesBabyy]

I've once taken 40 mg propranolol on an Ethylphenidate comedown. The effect I got was the complete opposite I had hoped for. I got extreme hypertension which was extremely scary.

(m)ethylphenidate and meth aren't the same thing, one is a reuptake inhibitor of DA and NE while the other is a very weak RI/strong releaser.

 

[ebola?]

You mean unopposed alpha agonism (as alpha and beta agonism tend to 'balance out' under pharmacologically 'normal' conditions, and adding a beta blocker to an adrenergic agonist can lead to disproportionate alpha activity). The main symptoms are actually dramatic vasodilation and troughs in blood pressure. This isn't too much of a danger with relatively moderate doses of adrenergic psychedelics (and even low to moderate doses of stimulants, really).

ebola

 

[Cyanoide]

You mean unopposed alpha agonism (as alpha and beta agonism tend to 'balance out' under pharmacologically 'normal' conditions, and adding a beta blocker to an adrenergic agonist can lead to disproportionate alpha activity). The main symptoms are actually dramatic vasodilation and troughs in blood pressure. This isn't too much of a danger with relatively moderate doses of adrenergic psychedelics (and even low to moderate doses of stimulants, really).

ebola

But this is anyway not something to recommend? Am I doing the right thing by discouracing users from mixing beta blockers and phenethylamines?

 

[ebola?]

Yeah. If you somehow stumble into high adrenergic activity, it is quite dangerous. And really, if you need a beta blocker to manage beta-adrenergic action, you are taking too high a dose of an adrenergic agent in the first place.

 

[Hammilton]

(m)ethylphenidate and meth aren't the same thing, one is a reuptake inhibitor of DA and NE while the other is a very weak RI/strong releaser.

Gee, thanks for the lesson. This isn't BDD. We don't need irrelevant restatement of everything we're already aware of.




For something that's a little more belonging here, I'd direct you to http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009019#pone.0009019.s005 and download Table S2. I didn't look real close, but I don't see any of these having much affinity at either alpha or beta receptors.

Not my favorite study by any means- you'll notice that according to that table MDMA has a Ki value >10,000nM @ SERT which is frankly unbelievable and contradicted by every other study I'm aware of. None of those have have affinities for these receptors- Lisuride excepted, but no one is using that as a psychedelic.

 

[ebola?]

Yeah, that study's pretty neat, but I think that it loses validity with high dose compounds (eg, it doesn't do well accounting for mescaline's activity as a psychedelic either). Perhaps someone with more math knowledge than I can demonstrate why re-deriving binding affinities from their constructed dependent measure will prove problematic when overall potency is low.

ebola