Make some GABA active chemical from Piracetam?

[Barney2]

Hi

I first apology for my English. I have guestion for someone with chemical experience. My idea is easy. As Piracetam is cyclic GABA derivative (with no GABA activity), is there any way how it could be "decycled" to a chemical, which would be GABA active (i.e. GABA agonist or GABA positive allosteric modulator)??

The core of Piracetam is 2-pyrrolidone. I think that 2-pyrrolidone could be "decycled" or decompossed by heat or with water? Have you any idea?

 

[jamesBrown]

I think this discussion might be better in the "Neuroscience and Pharmacology Discussion" forum. Maybe not, I'm not sure. But if I were you, I would PM a mod or admin and get their interpretation.

 

[sekio]

Piracetam could indeed by hydrolised to an open chain molecule. I'm not sure it would share piracetam's activity in vivo though. The ring opened compound would be expected to be a metabolite of piracetam in the body, I'd think.

We don't usually allow synthesis discussion on Bluelight, but this is innocuous enough as a theoretical question I'll let it pass.

Moving OD --> NSPD

 

[Solipsis]

There is a hydroxide needed to achieve the intermediary state towards the ring opened acid, not sure if water is enough. It isn't for lactones, right?
But the same reaction mechanism for lactones should work similarly for these oxopyrrolidines like in piracetam, or even better since a quaternary amine state is involved. Correct me if I'm wrong Seek.

Any objections against resulting N-substituted GABA analogues like that (in this case GABA N-acetamide or the associated aminobutyrate)? Picamilon suggests that there is no particular problem with something like that say passing the BBB, after all that is a major reason how picamilon was designed, but the acetamide doesn't have anything majorly non-polar like aromatism and surely looks more polar than nicotinoyl.
Hard to say for me what the BBBouncers would say about it, someone else would have to jump in if they can predict it.

I'd read up on picamilon because it could offer a lot of suggestions about what a BBB permeable form of GABA might be like. FYI, I like picamilon a lot and it is definitely not simply sedating or just a depressant like you would expect from 'anything GABA'd' or even taking an attack dose of pure GABA itself, well it isn't at least not at all doses of picamilon apparently. I doubt the niacin plays a pharmacological role there... I also am not sure how much of the N-substitution is expected to dissociate once in the brain i.e. whether it really matters what is hanging on the GABA molecule that allowed it to pass the BBB. But I'd say it's possible that the substitution could make for altered effects compared to GABA, who knows. Perhaps it couldn't hurt to investigate all the ring opened analogues of racetams. Although it may be that the racetam structures and substitutions are meaningless in this picamilon analogue investigation and it is better to start designing from there, or from scratch, modelling and whatever lead you can find.
The relatively long effects from picamilon (unless I'm mistaken) may suggest that immediate metabolism is prevented because dissocation into GABA is delayed. Oops no wait, short half-life... so purely subjective that it felt like the effects extended, less than phenibut but still similar in a way. Can be stimulating, I wouldn't take it too late in the day. Still IME it is nothing like the super transient effect of GABA.

 

[5_HT2A]

cant really read cuz im on a shit ton of tramadol. but phenibut is pretty much gaba with a phenyl ring. can get you high and helps so much with anxiety. i personally havent tried it though, not yet. ill probably get addicted to it.

 

[sekio]

Thanks for contributing to the discussion a whole bunch... I'm sure none of us were aware of phenibut's existience. And I, for one, would like to award you a medal - because being high on tramadol is such a unique achievement nobody's ever accomplished before.

anyway, the ring opened compound would look like this:

looks like a combiantion of GABA and glycine to me.

 

[Solipsis]

Might be interesting, doesn't glycine have a relaxing effect? - I believe theanine's effects are partially mediated by it. So that could mean dual action. But, if it is true that some part of piracetam is ring-opened in the body we would see those relaxant effects as metabolite effects of pira. And that is not what's observed.
Is it possible though that some of aniracetam's anxiolytic effects are related to this? Somehow I doubt that, it seems like it's of a different nature.

Another related question: what would be the expected effect or fate of γ-butyrolactam in the body i.e. piracetam without the glycine moiety? I don't count stuff like pyroglutamate in the consideration.