Highly Selective Centrally Acting a2 Alpha Adreno-receptor Antagonist Experience?

[acetylcholine]

The only compound that I know of that is ingested solely for its properties as an a2 antagonist is Yohimbine. Other drugs, such as Mianserin, also have strong a2 affinity, but a2 is not their sole intended target.

Problem is, a quick look at the IUPHAR database reveals that Yohimbine also blocks many 5-HT receptors. Therefore, one cannot completely define an a2 antagonist experience after ingesting yohimbine. Rauwolscine aka Isoyohimbine appears to be more selective for the a2 receptor than Yohimbine, though it still has affinity for some 5-HT receptors. Rauwolscine is also found in Yohimbe bark. Unfortunately, unlike Yohimbine, it is not sold at supplement stores as an isolated salt.

Other selective a2 blockers exist, but I doubt they are found outside of pharmaceutical labs; none are currently approved drugs. Idazoxan looks promising, but there is very little info on it.

Has anyone tried, experimented with, or otherwise investigated highly selective a2 antagonists? If so, what are the effects, especially central ones?

I, personally, like yohimbine as an occasional bizarro stimulant\appetite suppressant\random boner inducer. I'd love to find out more about similar drugs.

Thanks.

 

[LuxEtVeritas]

I do not believe RAU is significantly any more selective than YO, though they act on the a2 subtypes somewhat differently, the main difference being the ratio as relates to a2C. Subjectively most find little difference as relates to the 'feel' of either agent.

YO:
α2-adrenoceptor antagonist (pKi values are 8.52, 8.00 and 9.17 for human a2A, a2B and a2C receptors respectively)

RAU:
Standard α2-adrenergic antagonist (Ki values are 3.5, 4.6 , and 0.6 nM at cloned human α2A, α2B, and α2C-adrenoceptors respectively). Partial agonist at 5-HT1A receptors.

 

[Smyth]

I have to check this again, but in the recent paper I was reading I read that the alpha2-AR antagonist needs to be coadministered with an SNRI to really get the proper augmentation effect.

http://dx.doi.org/10.1016/j.nurt.2008.10.039

The trouble is there arent that many good SNRIs on the market, and SSRIs maybe wont work as effective?

Well my yohimbine tree bark is in the post so will comment later when some actual real world experience is on hand.

 

[LuxEtVeritas]

well being simply the abstract i can not say for sure regarding what is in the article, but I see no mention of a2AR at all in the abstract itself (though may other receptors are listed) and fail to see how such would play a role in optimizing an anti-depressant

also note, just so there is no confusion that the two are distinctly interchangeable, Yohimbe Bark Extract is NOT Yohimbine as they act reasonably differently

Yes, Yohimbine is the main active, but other actives in an extract that usually is around 8% will exert meaningful effect

To note i have in my research already worked with Yohimbine analogues that are optimized to express a far superior, viable theraputic index (positive attributes existing before negative ones become present in most all test subjects)

 

[Smyth]

The article I quoted is in the repository, but this one is for free:

http://www.nature.com/npp/journal/v29/n6/abs/1300418a.html

 

[bob_arctor]

well being simply the abstract i can not say for sure regarding what is in the article, but I see no mention of a2AR at all in the abstract itself (though may other receptors are listed) and fail to see how such would play a role in optimizing an anti-depressant

also note, just so there is no confusion that the two are distinctly interchangeable, Yohimbe Bark Extract is NOT Yohimbine as they act reasonably differently

Yes, Yohimbine is the main active, but other actives in an extract that usually is around 8% will exert meaningful effect

To note i have in my research already worked with Yohimbine analogues that are optimized to express a far superior, viable theraputic index (positive attributes existing before negative ones become present in most all test subjects)

But you would say that alpha-yohimbine is far worse than these other yohimbine analogues in regards to viable theurapetic index?