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Which Kavalactone is the MAO-B Inhibitor?

infraredz

BULA!
"Kava-kava extract was found to be a reversible inhibitor of MAO-B in intact platelets (IC50 24 microM) and disrupted platelet homogenates (IC50 1.2 microM). Structural differences of kava pyrones resulted in a different potency of MAO-B inhibition. The order of potency was desmethoxyyangonin > (+/-)-methysticin > yangonin > (+/-)-dihydromethysticin > (+/-)- dihydrokavain > (+/-)-kavain. The two most potent kava pyrones, desmethoxyyangonin and (+/-)-methysticin displayed a competetive inhibition pattern with mean Ki 0.28 microM and 1.14 microM respectively. The inhibition of MAO-B by kava pyrone-enriched extracts might be an important mechanism for their psychotropic activity."

http://www.ncbi.nlm.nih.gov/pubmed/9832350
 

Monkava'd

A spoonful of sugar makes the Awa' go down.
As said before, if I'm not to be mistaken the Mao inhibitor properties of said compounds in respect to what infraredz just posted might be responsible for many of the reported 'bowel movements' but this has yet to be proven or investigated. Though that is just another strange aspect of this earthy root and might be better suited for another discussion (bowel movements).
 

infraredz

BULA!
Keep in mind this was done in vitro, and the MAO-B inhibition was shown to be reversible which is much safer than irreversible MAOIs. Also, take into account the affinity of the ligand. Now, lower IC50 values will translate to higher affinity meaning more inhibition of MAOI-B.

"Kava-kava extract was found to be a reversible inhibitor of MAO-B in intact platelets (IC50 24 microM) and disrupted platelet homogenates (IC50 1.2 microM)"

Remember that the lower the number, the "stronger" the effect of MAO-B inhibition.

Take a Rx MAOI-B, for example, Rasagiline which shows an IC50 of 4.4 nM in humans. [http://www.scbt.com/datasheet-204875-rasagiline.html]

We have the IC50 value of kava (taking the lower of the two, just for illustration purposes) as 1.2 mM which translates to 1200 nM.

We can see the drastic difference with Rasagiline being extremely more potent in its antagonism/inhibition of MAOI-B and showing that while kavalactones possibly have some affinity for MAOI-B, it is not nearly close to the potency seen in prescription MAOIs.

Hope that makes sense and lays to rest any concern that anyone may have about MAOIs.
 

Monkava'd

A spoonful of sugar makes the Awa' go down.
Ahhhh, to be honest i'd had it in mind lately the possible interactions between different substances we would normally use in our daily lives in reference to kava; and that did create some concern (even though the natives have used kava for 3,000 plus years); but from what you've proposed by the substance just presented (Rasigiline) that concern is unwarranted, correct?
Given the lc50 values obviously being on a lower end of the spectrum.
And yes from that data it should be noted out of most substances that have adherence to being an mao/maoi or affinity to present receptors kava does not raise the red flags per se.
Thanks for clearing that up infraredz, you always deliver the facts.
 

infraredz

BULA!
Ahhhh, to be honest i'd had it in mind lately the possible interactions between different substances we would normally use in our daily lives in reference to kava; and that did create some concern (even though the natives have used kava for 3,000 plus years); but from what you've proposed by the substance just presented (Rasigiline) that concern is unwarranted, correct?
Well, no I wouldn't say that kava doesn't have the potential for adverse reactions to certain medications or substances. However, I was only stating that we shouldn't be worried about the fact that kava has MAOI effects.

And yes from that data it should be noted out of most substances that have adherence to being an mao/maoi or affinity to present receptors kava does not raise the red flags per se.
I'm not sure what you mean, but the issue of kava being potentially dangerous the average person due to its MAOI activity is next to nothing.

However, kava does have the potential to have adverse reactions with other medications, can aggravate some health conditions, and should always be consumed safely (from noble root only, using water) and you should always consult your doctor before starting any new substance, especially if you are taking other medications, have underlying health issues, history of health problems, genetic pre-dispositions to diseases, etc.


But this thread is about the MAOI activity of kava, and in that much, I can say it's safe to say that we don't have to take the same precautions that people on MAOIs have to (such as the strict dietary restrictions and such).
 

Monkava'd

A spoonful of sugar makes the Awa' go down.
Well, no I wouldn't say that kava doesn't have the potential for adverse reactions to certain medications or substances. However, I was only stating that we shouldn't be worried about the fact that kava has MAOI effects.


I'm not sure what you mean, but the issue of kava being potentially dangerous the average person due to its MAOI activity is next to nothing.

However, kava does have the potential to have adverse reactions with other medications, can aggravate some health conditions, and should always be consumed safely (from noble root only, using water) and you should always consult your doctor before starting any new substance, especially if you are taking other medications, have underlying health issues, history of health problems, genetic pre-dispositions to diseases, etc.


But this thread is about the MAOI activity of kava, and in that much, I can say it's safe to say that we don't have to take the same precautions that people on MAOIs have to (such as the strict dietary restrictions and such).
Sorry for not clarifying when saying that kava is more safe opposed to many substances just like you said we have to uphold a higher measure of concern; due in part and because of their stronger proclivities to mao or maoi property's; I hope that clears it up.
Now in regards to medications, especially ssri's I found this tidbit interesting but am still looking into it so will come to more of a conclusion once more rigorous research is attempted.
"Three kavapyrones, the natural compounds (+)-methysticine and (+)-kavain, and the synthetic racemate (±)-kavain, were tested concerning their action on in vitro uptake of monoamines in synaptosomes prepared from the cerebral cortex and hippocampus of rats. Both synthetic and isolated kavain potently inhibited the uptake of noradrenaline but none of the kavalactones efficiently blocked the uptake of [3H]-serotonin. Uptake of [3H]-noradrenaline was inhibited in the following order of potency: (±)-kavain = (+)-kavain (up to 70–80% of control)>(+)-methysticine. The results indicate a pyrone-specific non-stereo-selective inhibition of the [3H]-noradrenaline uptake which might be responsible for or, at least, contribute to the psychotropic properties of kavalactones [23]"
This is all in referral to a post made on a website about possible instigation of serotonin uptake which was proven not to be very much at all since dopamine was more likely to be affected during the time kava makes its rounds through the neurological pathways (outside of the cerebral cortex in specific) .
Though if the perspective is looked at from the standpoint of mao-b it's likely even that action is counteracted in the same way noradrenaline is inhibited.
What's really being shown about the interaction between kava and/or other ssri's is that it holds the possibility of unintentionally potentiating the ssris themselves leading to a danger of its own; not that kava in singular is a danger (just like alcohol in combination with other depressants for example) .
This at least helps Institute a better mindset in that for any of the negatives retorted with kava itself; therein lies the scientific practice to debunk that negativity sheerly through factual information and fabricate a more serious outlook on the substance.
 

Akava

Kava Enthusiast
Thanks for all the responses,

I wasn't concerned about the MAO activity, the reason I was curious was because I was considering using kava to inhibit breakdown of PEA supplement
 

Monkava'd

A spoonful of sugar makes the Awa' go down.
Thanks for all the responses,

I wasn't concerned about the MAO activity, the reason I was curious was because I was considering using kava to inhibit breakdown of PEA supplement
No worries Akava, I just got lost in the science. :bookworm:
I apologize if you felt I derailed your thread.
In response to your post; that's the first time I've heard of someone using kava in that way; but you never know.
This if possible would show its potentiality in many other contexts than have been investigated thus far.
And that drives me to learn even more. :pompus:
 

aviavieu

Kava Enthusiast
Keep in mind this was done in vitro, and the MAO-B inhibition was shown to be reversible which is much safer than irreversible MAOIs. Also, take into account the affinity of the ligand. Now, lower IC50 values will translate to higher affinity meaning more inhibition of MAOI-B.

"Kava-kava extract was found to be a reversible inhibitor of MAO-B in intact platelets (IC50 24 microM) and disrupted platelet homogenates (IC50 1.2 microM)"

Remember that the lower the number, the "stronger" the effect of MAO-B inhibition.

Take a Rx MAOI-B, for example, Rasagiline which shows an IC50 of 4.4 nM in humans. [http://www.scbt.com/datasheet-204875-rasagiline.html]

We have the IC50 value of kava (taking the lower of the two, just for illustration purposes) as 1.2 mM which translates to 1200 nM.

We can see the drastic difference with Rasagiline being extremely more potent in its antagonism/inhibition of MAOI-B and showing that while kavalactones possibly have some affinity for MAOI-B, it is not nearly close to the potency seen in prescription MAOIs.

Hope that makes sense and lays to rest any concern that anyone may have about MAOIs.
Selegiline has an IC around 8nm, kavalactons as you wrote 1200nm. When we drink 20g of Kava we drink 2g of Kavalactones together, and the dose of Selegiline is 10mg. So it does not come out that Kava is similar in MAO B power to Selegiline? Because it is dosed much higher. how to read it. Someone explain :)

Kava is about 150 times weaker MAO B, but it is also 200 times higher dosage from, for example, Selegiline.
 
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