Piperine - substance of interest?

[Snowy]

Piperine is a spicy alkaloid. A source is black/white pepper with content of about 4-7/5-9%.
Despite it's ubiquitary use as a spice in often not minor amounts, it's seems to have significant effects on the body. It's taste is awful and hence incompatible with most types of food.

Low level effects:
MAO-A Inhibitor: IC50=20.9µM [1]
MAO-B Inhibitor: IC50=7.0µM [1]
PGP/CYP4A3 Inhibtor [2]
Raise in piperidine levels of blood and brain [3]

High level effects:
CNS depressant effects for electroshock seizures[4, 5, and many other]
Lowering of NA in brain/raise of DOP in some parts/raise of 5-HT in some parts[5]
Antidepressant activity for chronic mild stress[6]

Facts and thoughts:
Piperine is metabolized pretty quickly into piperidine and other obvious metabolites (half life in human ~2h). Piperidine is likely to play a major role in it's effect, though it has stimulant-like effects.
It also enhances the bioavailability of various drugs, but this effect is not that interesting for me.

My experiences:
In combination with Methylphenidate it seemed to exhibit some stimulating effects, which were overall significantly stronger than the ones of MPH itself, but again somehow weird. On it's own (due to extensive use of multiple drugs at this time has just a limited meaning - but most other drugs should have had just a minor effect) it had some weird effects which were somehow sedating. I tried it in very different settings again, but the effects seemed to vary greatly and most likely depend strongly on the different plasma levels of other substances.
But anyway i wasn't able to assign a well defined profile to it. This sounds strange, but it's not difficult for me to do with other substances even in combination.
The doses i used ranged from ~100mg to 500mg. At first it was used pure, then just in form of pepper of which the piperine-content was known.

My questions:
In theory it looks like an interesting addon for multiple drugs - am i right?
Has anyone experience with it and combinations with other drugs?
More pharmacokinetic data on it?
What effects and half life has piperidine?
Do the other metabolites significantly contribute to it's action?
What do you think about this in general?


References:
1. Seon A LEE,a Seong Su HONG,a Xiang Hua HAN,a Ji Sang HWANG,a Gab Jin OH,b Kyong Soon LEE,a
Myung Koo LEE,a, c Bang Yeon HWANG,a and Jai Seup RO*,a
"Piperine from the Fruits of Piper longum with Inhibitory Effect on Monoamine Oxidase and Antidepressant-Like Activity"
Chem. Pharm. Bull. 53(7) 832—835 (2005)
2. Bhardwaj RK, Glaeser H, Becquemont L, Klotz U, Gupta SK, Fromm MF
"Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4"
J. Pharmacol. Exp. Ther. 302 (2): 645–50
3. B. GANESH BHAT and N. CHANDRASEKHARA*
"METABOLIC DISPOSITION OF PIPERINE IN THE RAT"
Toxicology, 44 (1987) 99--106
4. Eun Bang Lee, K u k H y u n Shin and W o n Sick W o o
"Pharmacological Study on Piperine"
Arch. Pharm. Res. 7(2), 127'--132 (1984)
5. A K I T A N E M O R I 1, H I D E A K I K A B U T O 1, AND Y I N - Q U A N P E I 2
"EFFECTS OF PIPERINE ON C O N V U L S I O N S
A N D ON BRAIN SEROTONIN A N D
C A T E C H O L A M I N E L E V E L S IN E1 MICE"
Neurochemical Research, Vol. 10, No. 9, 1985, pp. 1269-1275
6. Song Li a,c,⁎, Che Wang b , Minwei Wang c , Wei Li d , Kinzo Matsumoto e , Yiyuan Tang a
"Antidepressant like effects of piperine in chronic mild stress
treated mice and its possible mechanisms"
Life Sciences 80 (2007) 1373 – 1381

 

[dread]

You can make MDMA from it. I'm not gonna tell you how though (rules).

 

[chloral hydrate]

There's something to make it into piperonal that's all I know, from then I think it's like any substituted benzaldehyde> amphetamine.

MAO-A Inhibitor: IC50=20.9µM [1]
MAO-B Inhibitor: IC50=7.0µM [1]

^What does this mean? Can you find similar data for say phenelzine or selegiline see how it compares? Such an available MAOI would really be something.

 

[fastandbulbous]

You can make MDMA from it. I'm not gonna tell you how though (rules).

Yes, it's got a 3,4-methelenedioxyphenyl group in there somewhere, but it seems an awful lot of work to do so

 

[Snowy]

Obtaining MDMA is not of interest for me.
I'm mainly interested in the actions piperine.

I will search for some pharmacological data of some other MAO-Is later. But these are not really* conclusive for irreversible MAOIs (at least not as conclusive as would i wished it to be). Piperine is a reversible MAO.

* depending on the difference and some other factors...

 

[bpayne]

so this stuff is in regular table pepper?

 

[kakti]

Yes

 

[seep]

There's something to make it into piperonal that's all I know, from then I think it's like any substituted benzaldehyde> amphetamine.

MAO-A Inhibitor: IC50=20.9µM [1]
MAO-B Inhibitor: IC50=7.0µM [1]

^What does this mean? Can you find similar data for say phenelzine or selegiline see how it compares? Such an available MAOI would really be something.

I don't remember specific dosages, but some time ago I took piperine + curcumin + EGCG + 5HTP and felt like someone was dangling a bucket in front of my punting foot. Resting heart rate got up to 140 I think.

 

[seep]

There's something to make it into piperonal that's all I know, from then I think it's like any substituted benzaldehyde> amphetamine.

MAO-A Inhibitor: IC50=20.9µM [1]
MAO-B Inhibitor: IC50=7.0µM [1]

^What does this mean? Can you find similar data for say phenelzine or selegiline see how it compares? Such an available MAOI would really be something.

These IC50s are 3 or 4 degrees of magnitude higher than selegiline's (i.e. piperine's a much weaker inhibitor). Too lazy to look up phenelzine's values right now.

 

[bpayne]

how would you isolate the psychoactive ingredient from the pepper, or would it even be worth it to do so?

 

[chloral hydrate]

It is possible, look here. Scroll down until you see those yellow crystal like things- that's supposedly recrystallized piperine.

 

[Nibiru]

It works to boost different herbal medicines and psychoactive drugs, but not super dramatically. It's rather irritating, so you can only take so much of it. Besides, heavy enzyme inhibition from anything for almost any reason isn't usually a good idea, in my opinion.

 

[bpayne]

yeah, I'm totally retarded when it comes to a lot of biochemistry and pharmacology but I still read those types of things, so I can understand better, I get the concepts but I think it's all the math that gets me ( I was never good at math) and then putting it into practice would be difficult to me, considering how dangerous even a simple mistake could be, but I love the reference and teaching materials on these matters, because they are interesting, It would take a LOT of researching and mock practice, before I even attempted a simple extraction involving solvents simply because I'm inexperienced and quite prone to fuck ups with things I have no experience in, but I do love reading about this stuff, thats how we learn right?

 

[bpayne]

wow, it looks like it still has pepper in it, but that probably is leftover or biproduct of the synthesis. cool pic also good thread on macros, posting clear pics is way better than those blurry shit pics people put up!

 

[Snowy]

It works to boost different herbal medicines and psychoactive drugs, but not super dramatically. It's rather irritating, so you can only take so much of it. Besides, heavy enzyme inhibition from anything for almost any reason isn't usually a good idea, in my opinion.

What do you mean by boosting different herbal medicines and psychoactive drugs?
It's well known to increase the bioavailability of many drugs (of herbal origin too). Do you mean a different effect? What concrete drugs do you mean to be 'boosted' (what is meant by this? increasing it's plasma level,it's effects by MAO-I or something completely different?) by it? The general mechanisms are more or less known too, therefore a general discussion might not be very 'productive', although interesting
"It's rather irritating" - on it's own or in combination? On what dose? Can you be more precise?
"Besides, heavy enzyme inhibition from anything for almost any reason isn't usually a good idea, in my opinion." what's against inhibitors in general?!

yeah, I'm totally retarded when it comes to a lot of biochemistry and pharmacology but I still read those types of things, so I can understand better, I get the concepts but I think it's all the math that gets me ( I was never good at math) and then putting it into practice would be difficult to me, considering how dangerous even a simple mistake could be, but I love the reference and teaching materials on these matters, because they are interesting, It would take a LOT of researching and mock practice, before I even attempted a simple extraction involving solvents simply because I'm inexperienced and quite prone to fuck ups with things I have no experience in, but I do love reading about this stuff, thats how we learn right?

I like people getting interested

I isolated just a few grams of piperine in the beginning. After that i used white pepper (also encapsulated) of which i roughly determined the piperine content. The only difference should be an additional content of some essential oils and pharmacologically insignificant organic matter which likely slows down the piperine release a little bit.

I asking myself what role piperidine - one of the major metabolites of piperine - plays in it's effect.
I did find various data about piperidine. It's a releasing agent (for many things ...), being an agonist on the nicotinic receptors. It's a natural neurotransmitter especially connected to sleep and similar states.
Has someone a good summary of it's properties? The problem with piperidine is, that most references i found were rather old or of very limited value due to very special information.

If someone actually experimented with piperine, please give some info about it's effect and your setting.
A problem could be unreliable absorption (due food intake, body parameters, consistency/processing/manufacturing procedure/brand of the pepper might have great effect too (of course i always used fine powder of the same brand)), which results in more varying plasma levels than for other drugs, because of it's short half life and chemical instability.

It may take some time for me to be able carrying out experiments on my own again, so you're welcome to do it and share your results

 

[seep]

I asking myself what role piperidine - one of the major metabolites of piperine - plays in it's effect.
I did find various data about piperidine. It's a releasing agent (for many things ...), being an agonist on the nicotinic receptors. It's a natural neurotransmitter especially connected to sleep and similar states.
Has someone a good summary of it's properties? The problem with piperidine is, that most references i found were rather old or of very limited value due to very special information.

There's a detailed clinical account (2004) of the effect of piperidine on frogs: you may or may not have run across it:

Click Here

If nothing else, this is a great read. Sample paragraph:

Piperidine possesses only weakly toxic properties. On frogs of
30 grammes weight I found quantities of from 1 to 15 milligrammes
injected into the abdominal lymph sac utterly fail to elicit any symptoms
whatever. Even after 20 milligrammes frogs often presented
no abnormality, though some seemed to hop rather clumsily. After
the injection of 30 milligrammes in winter frogs and of 40 milligrammes
in summer frogs this clumsiness in movement became very
marked. The animal remains quite still unless disturbed, and the
head sinks down somewhat lower than is normal. When irritated
repeatedly it crawls away or makes short leaps, in which it falls very
awkwardly and has great difficulty in drawing up its hind legs.
Every movement is accompanied by marked tremor, especially of the
head and neck. When laid on his back the frog generally makes
one or two vain efforts to recover himself, but then lies quite still.

 

[Snowy]

The IC50 for iproniazid (first antidepressant ever?) on MAO is 12,9µM, whereas the on for piperine is 11,1µM on MAO.
The IC50 for selegelin is 0,0035µM on MAO-B making it roughly 2000x as potent in vitro.
But the low bioavailability of SEL might make them comparable though (SEL is ~400x as potent in comparison ?). Additionally piperine has many other interesting effects.

There's a detailed clinical account (2004) of the effect of piperidine on frogs: you may or may not have run across it:

Thanks!
I didn't come across it yet, but it is certainly not from the year 2004! I guess this report is about hundred years old (from 189?-190?).
It doesn't cross the BBB itself, but with the aid of piperine the BBB should let it cross. So there should be some central effects (stimulating?) of it. Besides it has been identified as a neurotransmitter already, which occurs centrally.
Piperine seems to exhibit some stimulating/convulsant properties because of piperidine...
These effects though aren't relevant (?) until a very high dose is reached, because piperidine isn't very potent.
Before that it acts like a weak sedative - but i'm not sure why. And somewhere between the dose for sedation and excitation the MAOB-I effect becomes important.

It's still very cloudy what effects piperine and piperidine have on the human body. Many things interact here while the metabolites play into this too. The dose dependant effects, which vary greatly demonstrate this complexity.

 

[seep]

I don't know where the fuck my head was re the 2004 thing. I love the way it's written though.

The synth for PCP (and a host of other substances) is just 2 simple reactions apart from piperidine, so I assume there are few cases of straight-up piperidine poisoning.

Wiki lists piperidines as CYP2D6 inducers. This is interesting as there are few readily available inducers of the enzyme. But the references are either defunct or in Swedish.

How is the molecule metabolized?

 

[jam uh weezy]

A source is black/white pepper with content of about 4-7/5-9%.

You can make MDMA from it. I'm not gonna tell you how though (rules).

Sorry I don't belong in these parts, but I found that highly interesting.

 

[dread]

Extasy from pepper, mmm. Watch out, if the government finds out they will ban peppers!