what is the subjective experience of taking an α2 adrenergic antagonist?

[tantric]

Rauwolscine being the obvious example. no, i have no plans on taking it. i know it causes hypotension and sedation. this is related to me attempting to puzzle out the unusual experience i had with injecting PDM-35. it *should* be speed, but it just wasn't iv. the warm feeling in my chest - blood rushing to the core, perhaps? i know it slowed down my heart rate. what would it feel like to have your adrenalin receptors blocked? could it make you feel overwhelmingly safe and relaxed? i called the drug 'calgon' after my first shot - that's just what it's like.

yes, i'm reasonably literate in neurochemistry. literally just enough to hurt myself.

 

[doxylamine]

To my understanding, α2 is an autoreceptor that regulates adrenergic release. Agonists like Clonidine at this receptor decreases the release of adrenaline/noradrenaline and so antagonists at this receptor should increase adrenaline/noradrenaline release and have some stimulant properties, and Rauwolscine does. Yohimbine has this mechanism of action too and is generally regarded as a pretty dirty, jittery, anxiogenic substance. I don't imagine other similar agents to be much different in terms of recreational value, I think it's a bit of a pharmacological dead end in that sense but then again some people find all sorts of crappy drugs enjoyable.

Blocking β-adrenergic receptors in my experience (Propranolol) only seems to settle the body down and no real effect calming the mind. It's great before public speaking, if you are overstimulated from caffeine, on the COMEDOWN ONLY of an amphetamine or are generally feeling pretty anxious/having a panic attack and need to quiet the body so you can focus on trying to quiet the mind. β-blockers are definitely nothing like a benzodiazepine however, that's for sure.

 

[Scrofula]

And the one med class my parents do NOT have lying around; there have been times I could've used a beta blocker.

You start shooting research chemicals and you've gone beyond my ample realms. But alpha2 antags should cause hyPERtension, no? Far from sedation?

Yes, OK, I didn't look anything up at all, I just remembered all this: alpha2's are pre-synaptic. So they'd dampen a response. Block those, and shit, seems like it could be dangerous if there was no other feedback to say the synapse was flooded. You could check your sugar maybe, expecting a . . . drop in sugar. That doesn't sound right. Stims usually shoot it up, at least in diabetic me, and this seems like a round-about stim.

 

[Scrofula]

I'm seeing a lot of stuff on NE systems and this, what, PhenFen drug you just have lying around to shoot in your veins?

Which then always gets me. Does anyone still around want to suggest a quick function of NE in the CNS to me, just for fun and my appreciation? It seems like such an arousal chemical elsewhere, but I'd think there'd be more nuance in your brain.

 

[tantric]

my bad. it seems counter intuitive that agonizing adrenaline would be calming, but now that i've read more about it, fine. and more than fine - xylazine is abused recreationally.

as to why i injected PDM-35, i bought it based on the best comparative review of the phenmetrazinalogues i could find. and yes, i looked for real journals first - only to run into a disturbing amount of info on herbicides. when i found smoking it disappointing, i reviewed the review, which specifically mentioned the rush associated with injection. i'm diabetic, so i always have needles.... besides, as far as i know i was the first person to experience dizocilpine. i ordered it from the JLF catalog. injecting pdm was nothing compared to that, but now we know it has little appeal outside animals testing, and poor animals.

after i took the shot, it was as if my bones had turned to caramel. i *swooned* back into my bed. when the rush passed i got in my chair, ate a bag of candy and throughly enjoyed a few hours of commercial free tv. that time was pure calgon - an escape from the world, but not into anything psychedelic. i would trade that shot for a shot of meth or morphine any day. when those are gone, they're replaced by craving and anxiety. it's almost like the pdm-35 is still with me somehow, like real mdma experiences, but not at all intense.

and no, they're not paying me, though i have noticed that the only supplier is now sold out.

 

[sekio]

A2 adrenergic antagonists are unpleasant from what I understand, think yohimbine.

 

[Volsam]

A2 adrenergic antagonists are unpleasant from what I understand, think yohimbine.

^^^ I find yohimbine to be pleasant, lightly stimulating and mood uplifting in low dose (around 10mg or less) and in the right combination of other supplements.

 

[sekio]

I've yet to hear a positive yohimbine report by someone who isn't trying to sell the stuff

On its own it seems pretty nasty.

 

[Coolwhip]

Hey Tantric, could you clear some space in your inbox so I can PM you.

Sorry for the off topic post everybody.

 

[tantric]

raw yohimbe extract also contains Corynanthine which "acts as an α1-adrenergic and α2-adrenergic receptor antagonist with approximately 10-fold selectivity for the former site over the latter" ... "This is in contrast to yohimbine and rauwolscine which have around 30-fold higher affinity for α2-adrenergic over α1-adrenergic...As a result, corynanthine is not a stimulant (or an aphrodisiac for that matter), but a depressant, and likely plays a role in the antihypertensive properties of Rauwolfia extracts. Like yohimbine and rauwolscine, corynanthine has also been shown to possess some activity at serotonin receptors"..."Yohimbine has high affinity for the α2-adrenergic receptor, moderate affinity for the α1 receptor, 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1F, 5-HT2B, and D2 receptors, and weak affinity for the 5-HT1E, 5-HT2A, 5-HT5A, 5-HT7, and D3 receptors.[13][14] It behaves as an antagonist at α1-adrenergic, α2-adrenergic, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, and D2, and as a partial agonist at 5-HT1A.[13][15][16][17] "
..."Rauwolscine, also known as isoyohimbine, α-yohimbine, and corynanthidine, is an alkaloid found in various species within the genera Rauwolfia and Pausinystalia (formerly known as Corynanthe).[1] It is a stereoisomer of yohimbine.[1] Rauwolscine is a central nervous system stimulant, a local anesthetic and a vague aphrodisiac.[1]

Rauwolscine acts predominantly as a α2-adrenergic receptor antagonist.[2][3] It has also been shown to function as a 5-HT1A receptor partial agonist and 5-HT2A and 5-HT2B receptor antagonist"

α1 receptor: Specific actions of the α1 receptor mainly involve smooth muscle contraction. It causes vasoconstriction in many blood vessels, including those of the skin, gastrointestinal system, kidney (renal artery)[13] and brain.[14] ...Antagonists may be used primarily in hypertension, anxiety disorder, and panic attacks.

α2 receptor: It is a presynaptic receptor, causing negative feedback on, for example, norepinephrine (NE). When NE is released into the synapse, it feeds back on the α2 receptor, causing less NE release from the presynaptic neuron. This decreases the effect of NE.Agonists (activators) of the α2-adrenergic receptor are frequently used in veterinary anaesthesia where they affect sedation, muscle relaxation and analgesia through effects on the central nervous system

β1 receptor stimulate viscous, amylase-filled secretions from salivary glands[4]. Increase cardiac output

THIS SHIT IS COMPLICATED

 

[JK25]

raw yohimbe extract also contains Corynanthine which "acts as an α1-adrenergic and α2-adrenergic receptor antagonist with approximately 10-fold selectivity for the former site over the latter" ... "This is in contrast to yohimbine and rauwolscine which have around 30-fold higher affinity for α2-adrenergic over α1-adrenergic...As a result, corynanthine is not a stimulant (or an aphrodisiac for that matter), but a depressant, and likely plays a role in the antihypertensive properties of Rauwolfia extracts. Like yohimbine and rauwolscine, corynanthine has also been shown to possess some activity at serotonin receptors"..."Yohimbine has high affinity for the α2-adrenergic receptor, moderate affinity for the α1 receptor, 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1F, 5-HT2B, and D2 receptors, and weak affinity for the 5-HT1E, 5-HT2A, 5-HT5A, 5-HT7, and D3 receptors.[13][14] It behaves as an antagonist at α1-adrenergic, α2-adrenergic, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, and D2, and as a partial agonist at 5-HT1A.[13][15][16][17] "
..."Rauwolscine, also known as isoyohimbine, α-yohimbine, and corynanthidine, is an alkaloid found in various species within the genera Rauwolfia and Pausinystalia (formerly known as Corynanthe).[1] It is a stereoisomer of yohimbine.[1] Rauwolscine is a central nervous system stimulant, a local anesthetic and a vague aphrodisiac.[1]

Rauwolscine acts predominantly as a α2-adrenergic receptor antagonist.[2][3] It has also been shown to function as a 5-HT1A receptor partial agonist and 5-HT2A and 5-HT2B receptor antagonist"

α1 receptor: Specific actions of the α1 receptor mainly involve smooth muscle contraction. It causes vasoconstriction in many blood vessels, including those of the skin, gastrointestinal system, kidney (renal artery)[13] and brain.[14] ...Antagonists may be used primarily in hypertension, anxiety disorder, and panic attacks.

α2 receptor: It is a presynaptic receptor, causing negative feedback on, for example, norepinephrine (NE). When NE is released into the synapse, it feeds back on the α2 receptor, causing less NE release from the presynaptic neuron. This decreases the effect of NE.Agonists (activators) of the α2-adrenergic receptor are frequently used in veterinary anaesthesia where they affect sedation, muscle relaxation and analgesia through effects on the central nervous system

β1 receptor stimulate viscous, amylase-filled secretions from salivary glands[4]. Increase cardiac output

THIS SHIT IS COMPLICATED

No no, you are making it sound complicated.
Bring it down to basics.

Imagine the natural release of adrenaline when on a rollercoaster, now just the opposite of that.

No wait, you can't just fathom that...it is not that simple.

Adrenergic release and/or antagonism through natural or bio-chemical or pharmaceutical means has implications within pre-synaptic and post-synaptic reuptake, production and release of adrenaline and also the molecular building blocks within certain neurons and includes neurotransmitter sites that is directly related to the other neurotransmitters involved in all adrenergic actions...

Oh my soul wait, you can't explain it in one paragraph.

This shit is complicated. Hahahahahaha!!!

 

[Scrofula]

Or you can look at my dog with Addison's disease. I can't figure out what exactly her "adrenal insufficiency" is: she's a pitbull but jumpy like a chihuahua, takes a glucocorticoid daily, and a shot of a mineral-steroid once a month.

If she doesn't get those, she . . . slows down, stops eating. How does that work? Also, how does a glucocorticoid extra dose help her on the fourth of July? Or when family visits?

I am confused by it.

 

[sekio]

Addison's disease is a disorder where the adrenal glands, located above the kidneys, to the lower left and right of the back, do not produce enough of the steroid horomones that they normally produce in healthy people. As a result you get all sorts of problems caused from insufficient levels of cortisol and the like, problems with hormones in general as well as sodium/calcium level problems and probably even more complex shit. Administering exogenous glucocorticoids and mineralicoticoids helps restore the normal balance of the body though.

JFK actually had Addison's disease, fun fact!

 

[Scrofula]

True, but trying to decipher the nuts and bolts of what's happening to my dog is not easy.
I mean, trying to follow the course of the hormones, all the systems involved, is pretty involved.

On the meds she's fine, just a big dumb ol' dog, afraid of everything.


And, I'm not an IV drug user, but I prep a subQ shot for my dog every month.

 

[Neuroborean]

And the one med class my parents do NOT have lying around; there have been times I could've used a beta blocker.

You start shooting research chemicals and you've gone beyond my ample realms. But alpha2 antags should cause hyPERtension, no? Far from sedation?

Yes, OK, I didn't look anything up at all, I just remembered all this: alpha2's are pre-synaptic. So they'd dampen a response. Block those, and shit, seems like it could be dangerous if there was no other feedback to say the synapse was flooded. You could check your sugar maybe, expecting a . . . drop in sugar. That doesn't sound right. Stims usually shoot it up, at least in diabetic me, and this seems like a round-about stim.

it's a 5 years old thread but... it's interesting enough, IMO.

in MY experience as a diabetic type 1 I was expecting yohimbe bark tea to rise my sugar levels...
the experience was the total opposite, it caused a drop in sugar levels, but not a dangerous one, in fact I consider yohimbe a great sugar blood level stabilizer/leveler. In my opinion what it really does is "upgrading" how fat cells are used in the body energy metabolism, it's some kind of express keto so to speak.

I absolutely LOVE yohimbe and consider it a great plant ally. It doesn't do shit in terms of side effects for me (perhaps some strange come-up anxiety, but not too much) and it increase my energy levels 5-10 fold, combo-ing with kratom it's a total success for me. It also causes a very noticeable mood boost/uplift.

 

[izo]

found yohimbe bark also to be rather pleasant, maybe the pure compound is something else.