An article about GHB derivatives

[Deleted member 170540]

Recently I posted some pictures about GHB derivatives I thought of in the random molecule drawing thread...

Researching the subject more, I found an interesting article on the subject. The binding affinities of several GHB analogs were measured in the study and one compound (HOCPCA) had an affinity for the GHB receptor that was 39 times higher than that of GHB itself.

The full text of the article can be found at http://jpet.aspetjournals.org/content/315/1/346.full

GHB is known to bind to both GABA-B receptors and GHB receptors. I think that the euphoric effects are caused by binding to GHB receptors because the GABA-B agonist baclofen doesn't usually cause euphoria.

The question is: It's said that the sedating effects of GHB are caused mainly by binding to GABA-B receptors. Would a selective GHB receptor agonist be a stimulant instead of a sedative? GHB receptors are excitatory.

I don't think these compounds will become popular recreational drugs though, as they are lot harder to synth than GHB itself...

 

[sekio]

I think I remember reading somewhere that GHB agonists are excitotoxins.

 

[Deleted member 170540]

That's bad news... Maybe a small amount of DXM or other NMDA antagonist would protect from the neuron damage.

Does GHB have to be actively transported to cross the BBB? It doesn't look very lipophilic. Obviously these compounds are not of much use if they only act peripherally.

 

[sekio]

GHB is small enough to make it across the BBB by simple diffusion (like ethanol) I think.

 

[Deleted member 170540]

The molecules here aren't big either... Maybe they would cross BBB too.

The study only measured the binding affinity, and didn't comment whether these compounds are agonists or antagonists at the GHB receptor. I wonder what taking a GHB antagonist would feel like.

 

[sekio]

T-HCA is apparently an excitotoxin. Wikipedia only knows of one antagonist which is apparently "anti-sedative" but also anticonvulsant.

[e] the antagonist is NCS-382, pictured above

 

[ex-amine]

That's bad news... Maybe a small amount of DXM or other NMDA antagonist would protect from the neuron damage.

Much easier take Magnesium (as NMDA antagonist/ neuro protection)

your ex.

 

[Transform]

Do you have a link to a source about that? I've just told myself that it's not significant enough to worry about when I do it as infrequently as I do, but if a magnesium supplement can be an extra layer of protection that's wonderful.

 

[ex-amine]

deepblue.lib.umich.edu/bitstream/2027.42/28723/1/0000544.pdf

in rats , but aren't we all partially rat ?

Also most people lack enough Mg in their body so it is always good to take it as extra supplement.
maybe Mg en minimal dose dxm combined ?