A bioassay-guided isolation of the ethanol extract from the fruits of Piper longum yielded a known piperidine alkaloid, piperine, as a monoamine oxidase (MAO) inhibitor. Piperine showed an inhibitory effect against MAO-A (IC50 value: 20.9 microM) and MAO-B (IC50 value: 7.0 microM). Kinetic analyses by a Lineweaver-Burk plot clearly indicated that piperine competitively inhibited MAO-A and MAO-B with Ki values of 19.0+/-0.9 microM and 3.19+/-0.5 microM, respectively. The inhibition by piperine was found to be reversible by dialysis of the incubation mixture. In addition, the immobility times in the tail suspension test were significantly reduced by piperine, similar to that of the reference antidepressant fluoxetine, without accompanying changes in ambulation when assessed in an open-field. These results suggest that piperine possesses potent antidepressant-like properties that are mediated in part through the inhibition of MAO activity, and therefore represent a promising pharmacotherapeutic candidate as an antidepressant agent.
Can some simplify this into layman's terms for me. I've been trying to figure out Ki values and ED50/IC50 etc...
For an average person, at what dose does piperine inhibit MAO(B and A) to a signifigant degree lets say comparable to selegiline????????
Neuroscience and Pharmacology Discussion
IC50 (required concentration to inhibit 50% of the enzyme) for segeligine:
1.7 uM (1700 nM) for MAO-A
6.8 nM for MAO-B
Piperine's not very potent, then. I would imagine that since it is also subject to metabolism and has to distribute itself through the body (remember IC50 is for concentration in a cellular environment and sayas nothing about dose or absorbtion) it is not that useful as a MAO. I would expect it could work in larger doses, however.
Piperine is slightly selective for MAO-B, less so than segeligine.
The Ki value is the dissociation contant, a measure of how much the chemical likes to bind to the enzyme as opposed to floating free. Lower numbers are stronger bonds. Keep in mind this number says nothing about efficacy (activating the protien), just binding affinity.
ED50 = Effective Dose, for 50% of the population
1microM = 1uM = 1umol/L = 1000 nM. M stands for Molarity and it is a measure of molecules per a certain volume.
I'm sorry but I'm still a little confused, if uM says nothing pertaining to possible dose(lets say hypothetically that piperine is not subject to metabolism)then how can you say whether it is not potent. It seems to me 1000x less potent than selegiline, which would mean well over a gram or grams would be required for sufficient MAO inhibition right?(Thats alot of NASTY concentrated pepperyness, like swallowing MACE)
One last question then... As I'm on a quest to find a decent(obtainable)natural MAO(B)I that isn't horrible tasting or hard to acquire(expensive), I was thinking of Rhodiola extract here's the summary of that...
The methanol and water extracts exhibited respectively inhibitions of 92.5% and 84.3% on MAO A and 81.8% and 88.9% on MAO B, at a concentration of 100 microg/ml. The most active compound (rosiridin) presented an inhibition over 80% on MAO B at a concentration of 10(-5) M (pIC50=5.38+/-0.05).
The present investigation demonstrates that Rhodiola rosea L. roots have potent anti-depressant activity by inhibiting MAO A and may also find application in the control of senile dementia by their inhibition of MAO B
So again it looks like it has even less info pertaining to possible dose/potency, can u estimate how it would fair compared with selegiling?
Last edited by (zonk); 31-05-2011 at 08:15.
Neuroscience and Pharmacology Discussion
The reason I say (know) piperine is less potent -
1. The IC50s are an order of magnitude higher than segligine (not a good thing). In practical terms this means the concentration must be ~500 times bigger for successful inhibition.
2. It's got a whole bunch of conjugated double bonds which are hammered on metabolically, whereas segeligine is a small, relatively stable organic molecule.
3. Nobody uses pepper medicinally (kidding)
Rosiridin has an IC50 of ~10 uM then so you are actually better off using piperine, assumiong both drugs have the same dose kinetics. (which they don't).
Have you looked into harmala alkaloids? Why do you need a MAOI?
THANX AGAIN! I know ONE of the isolated harmala alkaloids is actually an MAO(B)I unlike the rest which are for MAO-A. I'm looking for a natural MAO-B inhibitor or 1 that is both A+B. The reason is to concoct a natural(semi/quasi-natural) blend that I can take daily and that I can easily ingest to help boost dopamine as well as serotonin levels when combined with other natural products...
Last edited by (zonk); 31-05-2011 at 20:00.