selective GABA agent

[markosheehan]

out of all commercially availible benzodiazepines and related compounds which is most selective for GABAa subunits 2 and 3.?

if someone has a study on this matter please post it.

i am aware there are some new compounds out there like the TPAs which are very selective for 2 and 3 but I am looking for one that has at least some/little documented human use.


it think it ia clobazolam but there could be something more selective because its not even that selective for it.?

 

[clubcard]

Pyrazolam was designed to be α2/α3 selective. It has no α1 affinity (Ki >11000) and very little α5 affinity (Ki >1000). That is why it doesn't appear to be dependence forming. Not fun, but that was the whole point of the design.

 

[markosheehan]

Where did you get those ki values from.
I can't find them anywhere.

What are it's ki values for a2/3

How come people note some sedation with high doses if it has no affinity for a1?

 

[AlphaMethylPhenyl]

Pyrazolam is addictive yet. The least addictive benzo is usually thought to be Serax (oxazepam), as it's only a partial PAM.

If you have a condition that makes you wound up and worrying, relief from that state of mind (and body) leads to relaxation itself.

 

[markosheehan]

So you think the answer to my question in OP is oxazepam?

I don't think it very selective for a2&3 considering it still causes amnesia at regular therapeutic dosages.

Any thing else?

 

[clubcard]

α2/α3 selective ligands do not cause tolerance or dependence (or at least we couldn't induce dependence in animal studies). I haven't heard of anyone becoming dependent on pyrazolam because it isn't fun. If you are anxious, it helps. If not, why take it?

 

[AlphaMethylPhenyl]

Bluelight isn't the place to get recommendations for drugs.

Similar to so many SSRIs on the market, there are a fair number of benzos because each person has a unique CNS and they all differ significantly in manners that (to my knowledge) neuroscience has yet to parse out fully.

Even if we were that kind of website, it's a fool's game trying to

1) self-medicate with drugs
2) find a drug that will be best for one simply based on reading what little data exists

Again, Serax has a cohort behind it that holds it as the least addictive benzo. That doesn't mean it's safe to self-medicate with. At best it's something to discuss with a (real) doctor, not a bunch of strangers on the internet.

 

[polymath]

I remember reading some data of preclinical experiments with an anxioselective BZD agonist, and apparently some of the subjects felt euphoria as a side effect. So it is possible that they are psychologically addictive to some people.

 

[markosheehan]

well I have narrowed it down to quazepam, oxazepam and clobazam.(besides pyrazolam, but not much info is available about this.)

out of these 3 which is most selective for a2&3, or least efficacy?. my guess is clobazam considering studies show that it does not impair memory at all at 10 mg which is a effective anxiety dose. oxazepam does effect memory though at therapeutic doses.

the concern for me( and maybe others) is not short term amnesic effects(go away after drug is broken down), but after long term dosing permanent cognitive deficits which do not go away even after long term abstinence from the benzodiazepine. that is the concern that should worry most people who take these and people should strive for something that does not do this but still has thereaputic qualities.

 

[polymath]

Some people get a good anxiety relief by taking a large dose of sedative antihistamine daily until you get tolerant to the sleepiness-inducing effect but not the anxiolytic effect. It probably doesn't work for most people, but it did for my panic and anxiety problems.

 

[clubcard]

Any benzo with ANY α1β2γ2 or α5β2γ2 PAM will be dependence forming. I totally agree that people can become addicted to anything but almost all benzos (1,4 and 1,5) cause dependence. I'm not sure how effective SSRIs are but some people find beta blockers very effective. Buspirone has it's advocates as do first generation antihistamines. If it's a long-term problem then checking the long term efficacy is the starting point.