Mucuna Pruriens in water
 

Hey All
This is hot off the press:

A water extract of Mucuna pruriens provides long-term amelioration of parkinsonism with reduced risk for dyskinesias☆ Parkinsonsim & Related Disorders. Aug 2010.

If you can get past all the dang confusing acronyms the authors employ, the key thing to note is that mucuna provides "long term anti-Parkinsonian benefits" wonder what "long term" translation from rat to human entails?!?

Dopaminergic anti-parkinsonian medications, such as levodopa (LD) cause drug-induced dyskinesias (DID) in majority of patients with Parkinson’s disease (PD). Mucuna pruriens, a legume extensively used in Ayurveda to treat PD, is reputed to provide anti-parkinsonian benefits without inducing DID. We compared the behavioral effects of chronic parenteral administration of a water extract of M. pruriens seed powder (MPE) alone without any additives, MPE combined with the peripheral dopa-decarboxylase inhibitor (DDCI) benserazide (MPE+BZ), LD+BZ and LD alone without BZ in the hemiparkinsonian rat model of PD. A battery of behavioral tests assessed by blinded investigators served as outcome measures in these randomized trials. In experiment 1, animals that received LD+BZ or MPE+BZ at high (6mg/kg) and medium (4mg/kg) equivalent doses demonstrated significant alleviation of parkinsonism, but, developed severe dose-dependent DID. LD+BZ at low doses (2mg/kg) did not provide significant alleviation of parkinsonism. In contrast, MPE+BZ at an equivalent low dose significantly ameliorated parkinsonism. In experiment 2, MPE without any additives (12mg/kg and 20mg/kg LD equivalent dose) alleviated parkinsonism with significantly less DID compared to LD+BZ or MPE+BZ. In experiment 3, MPE without additives administered chronically provided long-term anti-parkinsonian benefits without causing DID. In experiment 4, MPE alone provided significantly more behavioral benefit when compared to the equivalent dose of synthetic LD alone without BZ. In experiment 5, MPE alone reduced the severity of DID in animals initially primed with LD+BZ. These findings suggest that M. pruriens contains water-soluble ingredients that either have an intrinsic DDCI-like activity or mitigate the need for an add-on DDCI to ameliorate parkinsonism. These unique long-term anti-parkinsonian effects of a parenterally administered water extract of M. pruriens seed powder may provide a platform for future drug discoveries and novel treatment strategies in PD.

Didn't Fiona say that here some time ago? That ld must have some unique qualities that allow for easy passage beyond the blood-brain

I am willing to try out this if only I knew how to make a water extra of seed powder...

Laura

Laura-
Just put the powder in a bottle and shake it. Read the mucuna threads.

Oops
 

Well, the synapses aren't quite firing as readily as they should today.
lol. Thanks- I essentially flunked HS chemistry, and it shows.

Laura

sounds like they got IT directly into a vein.

You are right
 

You are right. I forgot that I saw "parenteral" and did not look up the definition, but it does mean directly through the vein. Well, we hopefully have levodopa in a pump fairly soon, so I wonder if mucuna could be patented to be formulated and administered intravenously somehow as an alternative to levodopa? It would be nice to have other options if it turned out to be more beneficial and less demanding on our livers and kidneys.

Thanks for noting this!

Laura

Laura-
A patent on mucuna for PD was issued six years ago to a group of neuros including Warren Olanow, the most published neuro in the US. The hopeful might say that they will do something great. The cynical might say that it is a slick way to bottle up a threat to the established money.

delivery method?
 

Does this article clearly say that all drug candidates were administered in the same way, via the vein?

I would assume all candidates were administered in the same way, but if they were not, that could totally change things. Like if the levodopa were fed to the rats, it would have to go to the gut and be digested and metabolized before getting to the brain, and we all know what changes that process can wreak on the amount of drug getting to where it needs to be and when. If that were the case, it would hardly be comparable to directly injecting something into a vein. It would not be an apples to apples comparison.

Laura, could you provide a cite to this article when you get a minute? Thanks!

you can only get the abstract
http://www.prd-journal.com/article/S...104-5/abstract

why not sinemet parenteral. they likely used that method to give exact doses, likely difficult to get rats to eat all their drug laced rat chow.
independent of this study, it would cost a fortune to inject ldopa, especially in the elderly who would need help plus not like diabetes, you need to hit a vein. quite dangerous for the layman.
imho, they need to develop a better sinemet cr, a formulation that is more reliable/predictable.
i believe at least 2 companies are working on that. and there is a ldopa patch in the works.
how would parential delivery be easier on kidneys/liver, it still passes thru them.

i'm glad to see someone working on this but i thought many were already getting relief from mucuana? and even if they gave the recipe, rat dosages can't easily be extrapolated to humans and their BBB is much less developed.

rats to phase3 trial in what, 10 years? then what?

Not sure of researchers affiliations or intent
 

Apologies for not linking to abstract; thanks Soccertese for doing so. IMHO, a levodopa patch would be disastrous. I have not had a good experience with Neupro, not to mention it was pulled from the market because of a flaw in smooth release of the drug in a predictable, reliable way. I cannot imagine how a levodopa patch would be better unless they vastly improve the whole design; in my mind "patch" means "patchy" drug delivery.

As for improved Sinemet, we have it in the form of Duodopa and provided by Solvay....oh wait, silly me, Europeans have had it for almost ten years. It has passed all trials there and is now being studied in a longitudinal way. Why in the heck was it not fast tracked here? It is outrageous that the pump infusion American style is only in Phase III here- that means we may have relief here in like five more years. My neuro is still promoting DBS over the pump, and he is a young whippersnapper.

As for the mucuna study, I am encouraged that someone has provided a literature review on it and pointed out the research design flaws in light of what they have discovered.

From the full text:

Our study is the first to demonstrate that a simple water extract of M. pruriens endocarp powder with no additives has a superior effect to the combination of MPE+BZ on parkinsonism and that MPE alone is superior to LD alone or LD+BZ combinational therapy in terms of efficacy of ameliorating parkinsonism with dramatically reduced risk for DID. This result is consistent with the observations by Ayurvedic practitioners that PD patients treated with M. pruriens alone do not exhibit any significant DID

They are certainly not reinventing the wheel here, but the main thing they found is that relief appears to be superior to that provided by levodopa/carbidopa. Less of it is needed for superior relief, unlike Sinemet, it has other natural properties (yet unidentified) that ameliorate symptoms, it can be taken in a water suspension, and the big find is that patients who start using mucuna, not levodopa, do not suffer from dyskinesia. Long term use of mucuna in actual patients, not rats, in India substantiate this in a clinical setting.

I like the fact that no decarboxylization is needed with mucuna, so that is one less drug we would need (It is carbidopa and levodopa in Sinemet) to take. They think that mucuna has other natural properties besides levodopa that allow it to be metabolized into the brain more efficiently thereby reducing any peripheral levodopa in system or plasma build up which may trigger dyskinesia and otherwise leave one feeling crappy or nauseated from malabsorbed medication.

Why they are doing these elaborate tests intravenously on rats, I have no idea. However, I think it is the first step in trying to establish "proof" that a substance meets specific points before any further research can be systematically pursued in formulating mucuna as a doctor prescribed alternative to levodopa therapy with oral Sinemet.

Laura