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Muscimol: an Atypical GABA-A Agonist?

C

chemicalburn

Greenlighter
Joined
Oct 29, 2007
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So I've been thinking about experience reports from people who've eaten Amanita muscaria and the vast majority of the significant trips describe lucid dreaming-esque effects, "minds eye" hallucinations, and other such phenomenon NOT normally associated with GABA-A agonists like the benzos and barbs.

Does anyone know if muscimol leads to a significantly different signal transduction pathway or has any other mechanism of action that differentiates it from the more well known GABA-A agonists. I know ibotenic acid may be partially responsible for some of these effects but I thought that they were largely similar to those of muscimol (but more toxic). Muscarine isn't centrally active so I can pretty much discount its contribution. Are there other compounds that can describe the aforementioned effect?

Edit: noticed another thread posted a few hours ago on this same topic if a mod wants to move this there.
 
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Muscarine is solely a cholinergic alkaloid, its a quat salt though, AFAIK, so its not going to get past the BBB.
 
Muscimol is in a different class of GABA-A receptor ligands than benzos and barbiturates. Muscimol binds to the GABA binding site, thereby acting as an agonist and activating the receptor. On the other hand, benzos and barbs are not "true" agonists, but allosteric modulators that bind to a different site on the receptor and potentiate the response to agonists.
 
5-HT2 said:
Muscimol is in a different class of GABA-A receptor ligands than benzos and barbiturates. Muscimol binds to the GABA binding site, thereby acting as an agonist and activating the receptor. On the other hand, benzos and barbs are not "true" agonists, but allosteric modulators that bind to a different site on the receptor and potentiate the response to agonists.
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That explains a lot, thanks. So basically benzos and barbs increase the affinity for endogenous gaba.

Does anyone have access to any journal articles that would describe the functional selectivity of muscimol?
 
5-HT2 said:
Muscimol is in a different class of GABA-A receptor ligands than benzos and barbiturates. Muscimol binds to the GABA binding site, thereby acting as an agonist and activating the receptor. On the other hand, benzos and barbs are not "true" agonists, but allosteric modulators that bind to a different site on the receptor and potentiate the response to agonists.
Click to expand...


Never knew that. Explains why thujone doesn't cause benzo addicts to go into withdrawal.
 
chemicalburn said:
That explains a lot, thanks. So basically benzos and barbs increase the affinity for endogenous gaba.
Click to expand...

Yes, that is correct. This leads to an increase in open probability and mean open time of the channel.
 
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Apologies for reviving an old thread but, does anyone have any knowledge of the amount in mcg or mg that one would take of pure muscimol? I am apprehensive to try it due to the fact that it is reported to have put people into comas and caused death.
 
Muscimol doesn't selectively affect GABA-A receptors. It also affects GABA-C receptor. Though I have no knowledge of that particular subunit.
 
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