Recreational value of "Peripheral" BZD Agonists?

[Hammilton]

I'm wondering if someone can comment on the recreational value of the "Peripheral" BZD Receptor agonists? I understand that this is no longer the accepted term, but i can't remember the accepted one right now. mitochonrial BZD receptor maybe? Oh well.

I assume that their anxiolytic effect is due to increased cholesterol transport resulting in increased THP (alloprenanolone) production. THP has barbiturate like effects, but I imagine that the delayed and presumably decreased action will result in a smoother and thus less recreational effect.

Have self administration studies been completed on these, like emapunil?

 

[seep]

Where is the binding site? I mean on the molecule? The obvious functional groups these seem to share are a carboxamide and a phenyl (which are both also present in the N-methyl norazepams). I tried overlays of the PBR drugs given in wikipedia with 7-hydrodiazepam and didn't find too much harmony.

Two of the overlays aren't too ugly when you align the carboxamides with the 3' or 4' nodes on the phenyls.

I hope someone else furnishes info on this. Thanks for bringing it up. I remember reading something not so long ago about a pleiotropy (or the opposite--I forget the term) being possibly responsible for certain anxiety disorders (or for OCD).

 

[AlphaOdure]

Ugh, I did a search looking for information on Emapunil (& BZD antagonists)... & this was all I found: only questions, no answers! Anyone care to help revive this thread? Anyone have any info on this drug/class of drugs & their efficacy for the symptoms they're supposed to treat? Anyone have any comments (either speculation or from personal experience...) on their effects on anxiolysis & sedation? Or their relation to typical -A and -B GABAergic agonists? Or just other GABAergic PAMs in general, like barbiturates? Or just any general information on this drug and/or class of drugs at all... & their overall efficacy, effects, & psychoactivity?

 

[sekio]

The "peripheral" BZD receptor doesn't produce "classical" BZD effects as it is not part of the GABA receptor complex - from what I have read, agonists @ P-BZDr are anxiolytic via a totally different mechanism from "normal" benzos.

I think this class of drugs is still 5-10 years away from a marketable drug in humans.

 

[P A]

I understand that this is no longer the accepted term, but i can't remember the accepted one right now.

Translocator protein?

 

[Epsilon Alpha]

Translocator protein?

I think so, unless there are peripheral GABAA receptors expressing the binding site. Not really sure what he's getting at either.

 

[sekio]

Pretty sure Hammilton was talking about the TSPO.

 

[P A]

Not really sure what he's getting at either.

Well I think he's referring to the CNS neuromodulatory properties of the mitochondrial TSPO. Either way the P-BZD receptor is a cool topic. Actually, the word 'peripheral' is really misleading and way past its expiration date, as far as I'm concerned. We've been well aware of the TSPO's existence within the CNS for over a decade now.

Anyone interested in the recent literature on subject should consider reading this comprehensive review.

Also this.

This paper describes its potential therapeutic implications as a drug target for everything from cancer to dementia.

comment on the recreational value of the "Peripheral" BZD Receptor agonists

I (and many others, I think) find diazepam to be peculiarly recreational in comparison to other benzodiazepines. Whether this has anything to do with its uniquely high affinity for the TSPO is, to my knowledge, an open question - at least for now. The TSPO's capacity to mobilize neurosteroids and promote anxiolysis sure do point in that direction though...