Matabolism of L-Dopa
 

JohntPM from the HU Parkinson's forum suggested that I post this here. It is my first post to this forum.

This is a scientific research paper I wrote on the subject of suspected L-Dopa metabolism by Cytochrome P450 enzymes in Parkinson's disease. It lays out where we are on the understanding of the metabolism of L-Dopa, the areas that need clarification and the problems related to the development of potential synthetic CYP 450 inhibitors due to the risk of serious drug-drug interactions. A controversial solution may lie in the use of a the very effective, natural CYP 450 inhibitors in grapefruit juice.

It is a long and detailed paper on a complex and controversial subject. I have tried to make it as understandable as possible, so please try to read it right through to the end. Print it out to be able to read it several times if necessary.

You can distribute this to anyone you wish. even your neuro if he/she is open to discussion. I welcome critical comments from anyone who knows the field.

The file is here ....

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wriga,

Welcome to the forum.

The forum rules are that you have to make 10 (?) posts before you can make a link. The url below is, I think, the one you intended to make:

(PDF) The Metabolism of L-Dopa - are Cytochrome P45 Enzymes Being Ignored?

The great advantage of NeuroTalk is that a thread has a much longer history than on other forums. It is not uncommon for a thread to be added to five years after it was started.

John

Thanks for reposting the link,
John,

I'm not yet familiar with this forum, but still making good progress with inhibiting CYP3A4 with Grapefruit.

I've refined the useful dose to 150-250 ml per day
Also a mixture of Levodopa C/L and MP works better.
I take ¼ tab of 10/100 C/L + 100mg levodopa in the form of MP. The ¼ tab is just to get 2.5 mg of Carbidopa to inhibit the DDC enzyme. This also works for the MP. I take this 3 times per day: 8h, 1h30h and 21h. It's working very well, I'm practically free of symptoms.
When I was taking 1 full tab with GJ, I got dyskinesia. I think the MP releases levodopa more slowly so I dont get such a sharp peak after the dose.

WARNING TO THOSE NEW TO THIS PROTOCOL
Before you try this you must read about the dangers of this treatment if you take other drugs for conditions unrelated to PD. It's all explained in the scientific paper for which the link is given above by John. I cant yet post this link directly because I'm too new here. Strange rules ...

Hi
Just to clarify, the reason for the linking rules for newly joined members is to combat the unfortunate rampant spam links that forums are plagued by. We understand this can be frustrating for legitimate members, but hope that the absence of spam on our forums is a worthwhile result. :)

Thanks for the explanation. I would very much like feedback from anyone who tries this protocol. It takes about a week to get a significant stable effect. In my case this has been followed by a continuous gradual improvement. A word of caution: the substance in Grapefruit, furanocoumarins (20mg for a 200ml glass) must be given all the consideration you would give to any other drug. It acts to protect 50% of all drugs from being degraded by the enzyme CYP3A4 and has a long lasting effect, more than 24 hours. When taken in combination with levodopa, you will only get good results if you take it regularly. If you suddenly stop GJ, you may get what is known as a withdrawal rebound effect which shows up as severe increase in symptoms, much worse than before starting GJ. This kicks in 2 days after stopping GJ, and can be stopped by drinking a glass of GJ. As with other drugs, if you want to stop GJ, you must cut down gradually over several days

errare humanum est
In my latest reply, read 14h30 or 15h00 instead of 1h30.

The full text file of this research has now been updated.

The link address is unchanged.
You wiil find it the post by johnt.

Here is a link to wriga's "Experiment Findings" document:

(PDF) Inhibition of the Cytochrome P45� enzyme CYP3A4 increases the bio-availability of Levodopa

And the winner is Jeffreyn 🥂🥂😀😀😀

Even this counts as a post
.

Thanks for your help .

But you should also read the paper.
It's the result of 50 days of testing.

Please note: grapefruit juice (GJ) can increase the potency of some drugs, and this can have a dangerous effect on some people. Please see your doctor.

I have run an n of 1 trial on me to test the effect of an adding a dose of GJ to an existing daily drug regimen of 5 x 75mg Stalevo (levodopa/carbidopa/entacapone), 1mg rasagiline and 8mg ropinirole CR).

Attachment 10260

Let me explain the testing procedure adopted. I ran four tests, two were controls (75mg Stalevo, no GJ), 2 tested the impact of GJ (one was 75mg Stalevo and 100ml GJ; the other was 75mg Stalevo and 200ml GJ).

Each test involved going for at least 1020 minutes without the ropinirole and rasagiline, 510 minutes without Stalevo, and 360 minutes without food. This is too short a period of time to completely wash out these drugs, but it is thought to be long enough for their remaining residual impact to be limited.

Each test involved doing a lap top version of the side to side tap test every 10 minutes from 20 minutes before a dose until at least 190 minutes after a dose. Each test gives two scores, the number of taps in 30 seconds for each of the left and right hands. Higher scores are good.

https://www.parkinsonsmeasurement.or...eToSideTap.htm

In the over detailed graph above you can see plenty of noise (certainly no statistical significance is claimed). But the classic level, rise, plateau, fall, level pharmacodynamic signature as you go through a dose cycle comes through clearly. There is just a hint that the therapeutic duration is longer for the higher GJ dose.

More testing is required.

John