Which is more harmful C/L ER or C/L + COMT inhibitor

[gesundheight]

C/L does good job in relieving PD symptoms. But the benefits come at a cost. Which is in the process of synthesizing Levodopa into dopamine in the brain hydroxy free radicals get generated according to scientific literature, which contributes to the progression of the disease. While COMT inhibitors inhibit COMT enzymes. COMT is an important process for eliminating toxic or biologically active catechols and other hydroxylated metabolites. Using COMT inhibitors for long time could lead to liver failure. C/L extended release means more levodopa into the brain over extended period of time. If you suffer from fluctuations which treatment would you choose C/L ER, or C/L + COMT?

[park_bear]

I use both

pubmed.ncbi.nlm.nih.gov/111...

"In contrast, clinical trials with entacapone demonstrated no increase in liver enzymes above those observed with placebo. Further, no instances of acute liver failure or death attributed to the drug have been observed in post-marketing surveillance studies. Consequently, liver monitoring is not required with this agent. These data demonstrate that tolcapone is associated with a risk of hepatotoxicity but that no such risk has been detected with entacapone."

Regarding: >"the process of synthesizing Levodopa into dopamine in the brain hydroxy free radicals get generated according to scientific literature, which contributes to the progression of the disease. "

link.springer.com/article/1...

Disease Progression and Pharmacodynamics in Parkinson Disease – Evidence for Functional Protection with Levodopa and Other Treatments

From the full text which is behind a paywall:

"Despite concerns (1,36) about levodopa worsening disease progression there was no suggestion that levodopa accelerated the rate of progression in this DATATOP cohort which confirms earlier findings (35). Indeed levodopa appeared to have a protective effect. In vivo animal studies and clinical studies have failed to demonstrate an unequivocal toxic effect of levodopa (37,38). Rather than a neurotoxic effect of levodopa, we found evidence for a robust functional neuroprotective effect."

[Gcf51 in reply to park_bear]

Both, I assume, COMT and ER? but which COMT, tolcapone or entacapone. This is the first time I have heard of either, tolcapone or entacapone.

[park_bear in reply to Gcf51]

Entacapone. Surprised tolcapone is even still available. Opicapone is newer and better but more expensive.

Ir makes C/L more effective / longer lasting.

[Gcf51 in reply to park_bear]

Does it interact with B6 like carbidopa?

[park_bear in reply to Gcf51]

No it does not. Inhibits a different enzyme than carbidopa.

[Gcf51 in reply to Gcf51]

AI says it does.

[Gcf51 in reply to Gcf51]

Oops!!! that was Entacapone.

Does opicapone interact with b6?

Gemini AI says:

No, there is no known direct interaction between opicapone and vitamin B6.

Opicapone is a medication used to treat Parkinson's disease. It works by inhibiting an enzyme that breaks down levodopa, a medication that helps to increase dopamine levels in the brain.  

Vitamin B6, on the other hand, is a nutrient that plays a role in various bodily functions, including neurotransmitter production. While vitamin B6 can interact with levodopa, it does not appear to interact with opicapone.  

However, it's always important to consult with a healthcare professional before taking any new medications or supplements, especially if you have Parkinson's disease and are taking other medications. They can provide personalized advice and monitor for any potential interactions or side effects.  

[park_bear in reply to Gcf51]

Carbidopa inhibits DDC (dopa decarboxylase), while entacapone inhibits COMT (catechol-O-methyltransferase)

Regarding interaction with vitamin B6:

mdsabstracts.org/abstract/c...

"with and without oral COMT-I (Entacapone and Opicapone)... there was no significant difference in vitamin B6 between the COMT-I oral and non-oral groups."

I take vitamin B6 and entacapone together and they do not interfere with each other in my observation, whereas I definitely did notice interference between carbidopa and B6.

AI is not a valid research tool. Results delivered by AI are not to be trusted

[pdbuzzboard in reply to Gcf51]

techtarget.com/WhatIs/defin... I recommend extreme caution when using AI to research medical issues. A general search of Artificial Intelligence Hallucinations generates a wealth of information on the topic.

[Gcf51 in reply to park_bear]

Do you take Opicapone with every dose of C/L or just at night?

[JayPwP in reply to park_bear]

There were reports of entecapone disrupting gut microbiome and negative impacts on PD?

[gesundheight in reply to park_bear]

I don't believe in conspiracy theories, but I would be taking such studies with a grain of salt and I would be looking to who's funding them! Furthermore, there are other studies document the possible toxicity of l-dopa. Besides, just from pure biochemistry standpoint L-dopa generates hydroxy free radicals to make dopamine. Which causes oxidative stress the main cause of all diseases including neurodegenerative diseases. And if levodopa is neuro-protective where dyskinesia and other drug induced symptoms come from? Not to mention carpidopa which despite its benefits is a problem on its own. It irreversibly binds with vitamin B6 which essential cofactor in over 300 biological processes. I ant imagine that we blocking a natural biological process by medication, like entcapone or carpidopa, and assume nothing would happen!

[park_bear in reply to gesundheight]

You dismiss the studies you disagree with without providing any actual evidence to support your views. You claim that there are studies that do support you but you fail to link to any of them. As to levodopa hastening the arrival of dyskinesia, that has been debunked twice, first in an observational study of patients who never took levodopa, and then in an interventional study. The one issue that you raise that is valid is the effect of carbidopa on vitamin B6. I explain how to handle that here: healthunlocked.com/cure-par...

[gesundheight in reply to park_bear]

pubmed.ncbi.nlm.nih.gov/806...

sciencedirect.com/science/a...

[park_bear in reply to gesundheight]

The first study was a rat study that used 200 mg per kilogram levodopa in a single dose. Dividing by 8 to correct to equivalent human dosage we get 25 mg per kilogram. For a 60 kg person this would be 1.5 G. No MD prescribes that much levodopa in a single dose. Moreover, they state the resulting OH radicals may be neurotoxic, which is not the same as stating that they are neurotoxic.

In the second reference. they managed to coax OH radical generation by repeatedly administering the same 200 mg per kilogram levodopa overdose, in dopamine-denervated striatum only, after a single dose at this level was not sufficient.

I may choose not to spend additional time on this. If I decline to respond to future replies that shall not be taken as an agreement from me that such replies are valid.

[gesundheight in reply to park_bear]

One last clarification. I'm not arguing for one point or another. I'm just seeking an answer for the question in the subject. hopefully the answer would help myself and others. Obviously C/L + ENT has been working for you. Unfortunately it hasn't for me. I've been on C/L + ENT for more than 3 years and the on time continue to shorten and my PD continue to worsen. On top of that my latest blood test shows liver abnormalities my primary doctor says it must be my PD medication. It might be just me, but I have to listen to my body and seek another solution to extend my on time.