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About apigenin and how it displace Benzodiazepines

M

Mracid

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Jan 26, 2015
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I was reading that apigenin along with EGCG are able to displace benzodiazepines from their binding site, there was a Ki value with it and I was wondering if it was simply possible, with one's bodymass, to approximately count the minimal dose at which they start to fight over benzodiazepines. I also saw that they had a second order positive allosteric modulator activity at low doses, which is why I ask the first question, it would be nice to use either green tea or Lemonbalm as benzodiazepines potentiators but if they take their place I guess that the effect would not be as intense.
 
The thing is, flavonoids are poor drugs, they are quite polar and therefore don't get to a significant concentration for psychoactive effects. I think the effects of lemon balm and tea are actually mediated via other means.
 
Thanks! But if some1 made an extract of say 15g of camomille, drink 3-5cups of green tea and 15g of lemon balm as an extract. Could that be high enough of a dose?
 
The lemon balm actives are at loeast primarily, terpenoid as I understand it, not direct GABA agonists, (allosteric, definitely NOT glutamate-displacers like muscimol unless some are present but in such microquantities and/or poorly absorbed as to be utterly without effect physiologically).

Primary action as understood personally, is whilst I haven't charged deep into the numbers, are on GABA-transaminase inhibition, if apigenin is a powerfully binding uncompetitive antagonist, then it would not be much use as a defense against it to deploy a transaminase inhibitor such as can be found within lemon balm.

Also the caffeine in green tea would be somewhat antagonistic to benzodiazepines. I'd avoid caffeine altogether coming off a benzo taper, It will make you feel more anxious, shaky, insomniac etc. and lower the seizure threshold. None of which one would wish to do when coming off benzos.
 
GABA-T inhibition comes from rosmarinic acid from lemon balm.
Apigenin is a second order Positive allosteric modulator for the primary order positive allosteric modulator, at low dose.
It also displace the binding of Benzodiazepines Ligands by being a benzodiazepine competitive agonist with weak potency I believe at medium dosage.
And at last become an inhibitor of the release of GABA to its receptor along with a really low PAM activity which displace normal potent benzo thus reducing GABA current, while being a NMDA antagonist at that kind of dosage too, which is extremely high, not achievable unless using HARD concentrate in high doses.

So, rosmarinic acid=more GABA, Benzo=More reaction to GABA, Low apigenin=more reaction to benzodiazepines, Med apigenin= displacing the benzo and increasing GABA action with less intensity than benzo or endogenous BDZ R ligands.

My question was more clearly: Can we calculate the dose at which apigenin becomes competitive to benzodiazepines? I was asking because any dose under that limit of competition for the receptor would actually potentiate benzo thus increasing the effect of GABA and rosmarinic acid would increase its amount. Altho any dose over this amount would be counterproductive.
 
Also caffeine absolutely do not interact with GABA current, It only potentiate indirectly Glu receptors in the frontal cortx, sure perceptually it can look like it counteracts its effect while it is just overriding it.
 
i was using pure apigenin powder, not sure of purity, but i did take hefty amounts a lot more than one would ever get naturally and conclusion is, no, it didnt do anything. i was in hope to help with anxiety
 
Yes, I didn't mean to imply caffeine bound GABA receptors, merely that it can act as a FUNCTIONAL antagonist, rather than a physiological antagonist. Old term, I know, but in practice, someone who is physically dependent on benzos, barbs, carbamates, chlormethiazole, methaqualone etc., ingesting significant quantities of caffeine are not going to help them.

Which is IMO more important, in context, than effects, or lack thereof of directly affecting GABAaR ion channel gating.
 
Caffeine is known to induce a pseudo-withdrawal syndrome -- basically, some of its effects can mirror common symptoms of withdrawal or can markedly intensify withdrawal discomfort -- although it is more common to hear about this effect in the context of opioid addiction. I don't think the interaction with GABAergics actually fits the definition of functional antagonism -- a functional antagonist would precipitate the withdrawal syndrome, as opposed to enhancing some of the symptoms. When benzodiazepine-dependent individuals take caffeine, is it common for them to have seizures? As far as I've heard that isn't a problem, but maybe soneone could enlighten me if that isn't true...
 
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yes caffeine can cause siezures withdrawing from benzos or alcohol, personal experience here. caffeine is one nasty ass substance!
 
Has anyone tried alive in to aid in their benzo taper. There is a gentleman in the UK that helps people reduce benzo usage.
 
Echoing Sekio's point, flavinoids are terrible drugs. We have co-evolved with plants producing tons of bioactive flavinoids, and have tonnes of metabolic enzymes which shred them.

Also if these were present in concentrations high enough to have benzodiazepine like effects, it would be counter productive to add them to a taper.


benzotrol said:
Apigenin, not alive.
Click to expand...
 
Skorpio said:
Echoing Sekio's point, flavinoids are terrible drugs. We have co-evolved with plants producing tons of bioactive flavinoids, and have tonnes of metabolic enzymes which shred them.

Also if these were present in concentrations high enough to have benzodiazepine like effects, it would be counter productive to add them to a taper.
Click to expand...
so maybe there's the possibility of inhibiting those metabolic enzymes to make the effects greater like we can do with MAO inhibition or oilahuasca enzyme inhibition to activate allylbenzenes??
 
Neuroborean said:
so maybe there's the possibility of inhibiting those metabolic enzymes to make the effects greater like we can do with MAO inhibition or oilahuasca enzyme inhibition to activate allylbenzenes??
Click to expand...
Are there reports of oilhuasca actually working and producing psychadelic and not delerient effects?

The protocol below seems to jump to a lot of conclusions, and I am wary that this would actually work.

Oilahuasca Activation - HerbPedia

herbpedia.wikidot.com herbpedia.wikidot.com
 
Skorpio said:
Are there reports of oilhuasca actually working and producing psychadelic and not delerient effects?

The protocol below seems to jump to a lot of conclusions, and I am wary that this would actually work.

Oilahuasca Activation - HerbPedia

herbpedia.wikidot.com herbpedia.wikidot.com
Click to expand...
I've read several reports of some of the attempts working, as well as some other not happening.
In those on which it didn't work supposedly it was because of something lacking or something extra added that spoiled the bio-assay. It's difficult for me to really know if it's bullshit or not as it seems very complex but in a way I think it's not implausible.
Personally I didn't try it but I would whenever possible, it seems pretty complicated/complex but I don't think it's too expensive to give it a couple tries.
Most reports are in dmt-nexus and other forums like that.
 
Neuroborean said:
I've read several reports of some of the attempts working, as well as some other not happening.
In those on which it didn't work supposedly it was because of something lacking or something extra added that spoiled the bio-assay. It's difficult for me to really know if it's bullshit or not as it seems very complex but in a way I think it's not implausible.
Personally I didn't try it but I would whenever possible, it seems pretty complicated/complex but I don't think it's too expensive to give it a couple tries.
Most reports are in dmt-nexus and other forums like that.
Click to expand...
I guess my biggest qualm with this proposed pathway is that some of the intermediates look like things that would either from an epoxide from the double bond opening, or be a Michael acceptor (the phenyl vinyl ketone intermediate).

Both of these would be liable of acylating proteins and the epoxide could likely acylate nucleic acids.
 
Skorpio said:
I guess my biggest qualm with this proposed pathway is that some of the intermediates look like things that would either from an epoxide from the double bond opening, or be a Michael acceptor (the phenyl vinyl ketone intermediate).

Both of these would be liable of acylating proteins and the epoxide could likely acylate nucleic acids.
Click to expand...
I was using wiki for some time trying to make sense to what you said, but my lack of enough technical understanding doesn't let me to fully comprehend what you're saying (I kinda get it, tho).
so your opinion is that none of those intermediates could form any real nitrogenated compound so it wouldn't be an alkaloid? I also think it doesn't need to be an alkaloid, to be active, because some people finds elemi oil very active on its own (and then the oilahuasca proponents think that it's because of their own personal enzyme profile...)
editing: but well, I don't know if those type of acylating compounds would do anything active and not unhealthy?
 
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Neuroborean said:
I was using wiki for some time trying to make sense to what you said, but my lack of enough technical understanding doesn't let me to fully comprehend what you're saying (I kinda get it, tho).
so your opinion is that none of those intermediates could form any real nitrogenated compound so it wouldn't be an alkaloid? I also think it doesn't need to be an alkaloid, to be active, because some people finds elemi oil very active on its own (and then the oilahuasca proponents think that it's because of their own personal enzyme profile...)
editing: but well, I don't know if those type of acylating compounds would do anything active and not unhealthy?
Click to expand...

I don't think it's impossible that some amines could be formed by a transaminase, but I feel like even inhibiting/inducing a handful of enzymes (and many of the compounds listed aren't strong mechanistic inhibitors), there are a lot of other places for loss to other metabolic processes (the body is very redundant in metabolism, think of how even taking the drug cimetidine (a mechanistic cyp inhibitor) doesn't seem to enhance the effects of opioids in even a two fold manner.

I guess what I was getting at, as some of the intermediates seem to have reactive groups ie the phenyl vinyl ketone intermediate, or the possibility of forming reactive intermediates (ie the parent compound being oxidized to an epoxide at the double bond, which is a pretty classic cyp450 transformation/toxification), which you wouldn't want in your body.

Probably not a big deal if done once or twice, but it could be bad with habitual use.

In general I am very skeptical of complex explanations where people read a bunch of papers and string them together to get from A to Z without throurough validation. Each assumption has some probability of being correct and when you string enough together, the likelihood of the whole hypothesis being felled by one wrong component becomes rather large.

Now if somebody who oilhuasca works for say took a selective 5ht2a blocker and the effects disappeared, I'd be on board (especially if they took say elemicin and the antagonist and still got effects).
 
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