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Non competetive GABA-A antagonist thujone for benzodiazepine tolerance?

M

Memantine

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May 16, 2015
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It has already been shown that the BZD receptor antagonist flumazenil rapidly reverses benzodiazepine tolerance.

But since flumazenil isn't easily obtained I was wondring if a low dose of the non compepetive GABA-A antagonist thujone might have a similar effect on benzodiazepine tolerance.
 
gabapentin def makes any bezo stronger im ny experience really I think taking precaution is warented if u r on benzos lets say n get gabapentin u don't know how much stoger it eill be for u so please becareful
 
im always getting involved with such topics related to benzo tolerance and potentiation and such, do alcohol works similar in that regard? instead of making separate thread about it asking the same damn thing, can it just be related/connected? that is, i did read gabapentin doing similar things for alcohol abuse, i hope its interconnected somehow
 
What you are proposing won't work and is a very bad idea. Flumazenil can reverse BZ tolerance because it is a neutral antagonist of BZ receptors. But another key element of the pharmacology of flumazenil is that it is a partial agonist of GABA-A receptors containing gamma2 subunits:

http://www.ncbi.nlm.nih.gov/pubmed/8913369

Giving a BZ antagonist to someone dependent on a BZ would normally precipitate withdrawal and induce seizures. However, the partial agonist activity at gamma2 (a non-BZ subtype) seems to suppress BZ withdrawal, explaining why it is possible to administer flumazenil to BZ-dependent individuals without causing seizures or other withdrawal symptoms.

Thujone is a noncompetitive GABA-A agonist. All it would do when combined with a BZ is cause seizures, anxiety, and other symptoms of withdrawal.

Thujone also isn't a great choice for administration to humans in terms of toxicity. PTZ is a better candidate. But neither one should be taken for the purpose you proposed.
 
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Yes the only safe way to administer small doses of this one is concurrently with something that heightens the seizure threshold even as volatile as ethanol I remember reading somewhere.
 
Yeah it seems that thujone is toxic over doses of 7mg, and that it additionally could have a negative impact on cognition as a nAChR antagonist at a7, the same subunit that a potential medication for cognitive impairment in schizophrenia activates.

As serotonini2A suggested, too, the utility of drugs is based on more fine details, but it's a good question.

Playing around with GABA antagonists without medical oversight and while dependent on BZDs spells trouble all over.
 
I have also read something about PKA inhibitors that block the BZ receptor binding site phosphorylation patterns mediated by cAMP-dependent protein kinase A (PKA), thus preventing receptor uncoupling from developing.


Can you clarify this? Is there some easily available PKA inhibitor around? Or are they toxic?
 
PKA has many different functions, so you wouldn't want to try to alter its activity. There aren't really too many drug-like compounds available to inhibit it.
 
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