Levodopa not working

Hi all. My dad has been diagnosed for 12 months and isn’t responsive to levodopa. Apparently only 10% of the population are not responsive to this drug. The one time it’s worse to be unique I guess? Has anyone encountered this issue and what avenues did you go down to find something that worked for you. Was it purely trial and error or is there something out there which is used for people specifically who don’t respond to levodopa. Can you help please. All responses are appreciated.

Thanks everyone.

Hi @LJT2302,

Parkinson’s affects everyone differently and there are no hard and fast rules when it comes to starting medication for Parkinson’s. In the case of your dad, I would recommend that you raise your concerns with his GP or Parkinson’s nurse so that they can look into his medication so that they can either increase his dosage or explore prescribing him a different type of Levodopa.

We have a lot of information on our website about Levodopa that may answer some of the questions you may have, also our head of Research Communications and Engagement, Claire Bale, has written a blog post answering the most frequently asked questions about Parkinson’s related medication. You can find both sources of information below:

https://www.parkinsons.org.uk/information-and-support/levodopa-co-beneldopa-and-co-careldopa

Along with our members who I’m sure you’ll hear from shortly, please remember that you can always give our helpline a call and speak to one of our advisers for more support on this.

Best wishes,
Reah

Levodopa does work for me, but it does not I believe slow the progression of PD, it helps mitigate its symptoms, what symptoms is he most bothered by & perhaps I can tell you what I use?

As for slowing the progression of the disease, there is only one thing (beyond exercise & diet) that I truly believe is working for me in staving off further progression, and that is Ambroxol - an old cough medicine that I take in a higher dose. I have included a link for some information about it:

https://www.centerwatch.com/clinical-trials/listings/168579/parkinsons-disease-dementia-ambroxol-as-treatment-parkinsons/

One quote from it: “using the drug Ambroxol, an agent considered safe enough to give to pregnant women, which has improved GCase function in pilot studies in humans. This strategy could stop or reverse the underlying pathology of PD; it might allow patients to get better.”

Here’s hoping it does, so far it is for me at 6 months and taking about 600mg per day.

@DHP thanks for the response. So he has quite significant arm tremours to the point where he can’t hold a cup or carry a plate without spilling things (had to resort to a flask now). Have you had this symptom? I will be sure to take a look at the Ambroxol research you provided as I’m trying to get him into the habit of visiting the specialist with more background knowledge so he has the ability to challenge the doctors on certain topics if needs be as he has not been treated greatly over the past 12 months (very poor communication between our GP and the specialiast).

Thanks again.

for tremor does he take?
Propranolol (beta blocker) 20mg (might need 2x daily)
Amantadine 100 mg 2x daily (recommend timed release if he can get it)

On the supplement side, highly recommend
Avena Sativa (green oat grass) 2 caps daily 800 mg total
Oyster Shell Calcium 2 caps daily (he needs Calcium, Oyster Shell said best for tremor)

Lastly
Full Spectrum CBD Oil

Oyster shell aside, if he uses the other 4 of these treatments daily, I’m fairly certain he can regain a good amount of control over his tremor, I do. For all reading this post, let me ask you a question, if I had an online Rx store specifically for Parkinson’s patients where all these items were available to you in 1 place. would that be of interest to you? Thinking about it, I already have Ambroxol available in my online store for any interested in trying it now before their disease (& mine) progresses further. In France you can get it over the counter, that’s how safe it is considered there.My confusion is why anyone who knows about it would be waiting for all the trials to complete in a couple of years when the might be able to slow or stop the progression now (?).

PS If you use Valerian Root at night before you go to bed (3 caps), it not only helps you sleep, but you should wake up with the mildest tremor of the day to start out. (You can use it during the day to control tremor, but it willl make you sleepy, so don’t drive & don’t try to lead any high powered stress laden meetings if you do. But if your tremor is really bad, I would consider it.)

Hi, the research into Ambroxol looks very interesting. Please excuse my ignorance because I’m new to this, but is the suggestion that it might only be useful for a particular form of Parkinson’s? (single GBA gene mutation)
If so, how do people find out whether or not this type affects them?
Thanks

Good question, and I’m glad you asked it, as it could be one of the few reasons I can think of as to why more people with PD haven’t tried Ambroxol, the others being:

1st awareness of Ambroxol as a significant treatment option or lack thereof seems to be a main reason why more people with PD aren’t trying it – that we will need to address in forums just like this one to get the word out to do your due diligence. If you ask me why you haven’t heard more about it, I would suggest to you that the big pharmaceutical companies have a huge role in what you know about, and since there is really no money in Ambroxol for them, they’re not going to promote it. The money is in drugs that have patents, not 50 year old repurposed cough medicines.

2nd there are trials underway that won’t complete for some time yet, so you might say the jury is still out on just how well it will work to slow PD progression – that said, given its safety and the positive results of trials completed to date, why wouldn’t someone with PD at least try it?; for me it is critical that you slow or stop this diseases’ progression as soon as you can, at a later state with much worse symptoms, I’m not sure how much of that damage you can reverse. This is a 50 year old cough medicine found to be I believe safe for pregnant women to take at the PD trial dose, should a person with PD really wait maybe 2 more years to try it when by then they could have dementia? In my view absolutely not. For me at least, enough of the jury is in for me to take an old cough medicine; I cannot and will not wait another 2 years to try something that is available now, is safe (at least for me to-date from 6 months of taking it, and from my research on it), inexpensive (dare I say cheap?), and could really work on my PD now (and so far is), my disease is certainly not waiting.

A 3rd reason could be that in the UK at least its hard to find a reputable place to buy it, as it is not sold in UK drug stores. Well, you could go to France where it is an over the counter medicine and buy it, or simply find it online from a variety of sellers from very different countries (I believe in it so much, I even started an online store for it). As always, do your due diligence on Ambroxol, potential side effects, completed trial findings, etc., and talk with your neurologist about it, I did. My doctor read the research and basically said go ahead if I wanted, and I’m extremely glad I did. Every day when it clears away the PD fog, mitigates my shoulder pain, and gives me a little more motor control, I’m reminded of just how glad I am that I did, and did not wait. .

As to your question, will it help me if I don’t have the PD gene? Here’s what the findings from the recently completed trial say (link attached): “Findings In this open-label clinical trial of 17 patients with Parkinson disease, Ambroxol crossed the blood-brain barrier and bound to the β-glucocerebrosidase enzyme, and it increased β-glucocerebrosidase enzyme protein levels and cerebrospinal fluid α-synuclein levels in patients both with and without glucocerebrosidase gene mutations. Meaning Ambroxol therapy has potential for study as a neuroprotective compound for the treatment of patients with Parkinson disease both with and without glucocerebrosidase gene mutations.” Essentially for me the answer to your question from that is yes, it could help you whether you have the gene or not.

https://jamanetwork.com/journals/jamaneurology/fullarticle/2758317

My apologies for the long winded answer, but I have to admit I have been very confused by just how few have tried it given its potential PD life changing outcome, and needed to put that out there for community thought.

Again, thanks for the question!

DHP…your information is invaluable, and I thank you for it. One question that I have, is this…Since it appears from your account that Ambroxol is exhibiting evidence of repair work in the brain ( dare I suggest attacking amyloids of misfolded alpha syneucleon), what is your reasoning for maintaining your intake at the level you are now taking ? Why not take a further 500mg/day as the initial trial identified as a target study concentration?

excellent question, and I plan to do just that starting next week. I believe there is a trial now planned at the roughly 600mg daily level to see if it gives app the same result as the 1,100mg level trial just completed. Since I am my own trial (good for me!), I started myself out escalating to the 600mg level to see what that did for me. Well, it did good things. Will another 400 or 500mg do even more for me? that’s what I now plan to find out. I should have a clearer picture going up in dosage as to what it does for me than I would coming down, that was my reasoning at the time (that plus 600 mg a little more cost effective if it does app the same thing, & really not fond of taking 3 rounds of pills every day if I don’t have to, but I absolutely will if there is a gain to be had). So stay tuned. Thanks again for the question!

DHP - thank you for your very comprehensive reply.
I see from one of your previous posts on this subject that you also keep the syrup as a back up
I think that for many people, me included, the sheer number of tablets needed is off-putting.
Are there any particular reasons for not taking the syrup instead?

Jgo With DHPs exciting revelations, can you keep step with her through relaying what syrup manufacturer can reliably provide the high Ambroxol concentrations that can see us build up to 600mg/day, then, maybe as much as 1.2 g/day of ambroxol…naturally the fewer spoonfuls the better ? I’ve not taken medicine in syrup form before. Do amazon offer high concentrations ? A further note of caution to all readers…it is important to research what other Parkinson’s medications (which you may be taking) are NOT compatible with Ambroxol…eg ,as I gather, Rasagaline

Hi William,

Unfortunately I don’t have the answers to your questions but they are definitely things I will be looking into if the syrup looks viable as a way of taking a large enough quantity of the drug.
Yes, of course people have to be careful not to take something that might interfere with other medication and I would talk to my doctor before taking anything, but I’m not not currently on anything else.

Hi,
I’m excited about this!!! thanks for posting.
I want to get Ambroxol but cant find it on Google. can you post a link to your supplier.
Thanks
All the best,
Alan

Tablet form is available on Amazon for one, and I can point you to other places as well, including of course French drug stores. Full disclosure, I believe in this product so much I started a company to get it out there to people with PD, that is who sells it on Amazon UK from a French manufacturer - we need access to it now, not years from now when our PD is worse. I have also seen it available from Russian, Vietnamese & Thailand sources on ebay, but really can;t speak to their product quality one way or the other.

yes, it is extremely exciting, and trying my best to get people with PD to do their due diligence and decide for themselves, absolutely working for me. If I can help further, just let me know.

that could be alot of syrup. I’ve gotten used to the pills, in fact I chew them up and then swallow, a bit harsh, but I found a small piece of your favorite chocolate after solves that problem. I have to tell you, when I chew 10 tablets up in the morning, my PD brain fog is gone in an Ambroxol rush, very impressive and heartening, not to mention my shoulder pain disapates soon thereafter.

for me the pills are really the way to go, small and easy to chew (or swallow a couple at a time), the syrup equivalent would be too much syrup for me, but I am thinking about asking our French manufacturer if they can add some lemon (what else do you like?) to the tablets, as if you chew them they can be a bit harsh, although when I do that the almost immediate brain impact for me is quite impressive. If you all still really want the syrup option, I will check with the manufacturer and see what they can produce for us ???

DHP, from my observation, the available syrup alternatives do not provide Ambroxol in attractively high concentration, for the purpose that we, with PD are ‘wanting’ to utilise/investigate the chemical…thus, as you say, large volumes of fluid would require consumption, and the 30mg pill option to me seems best choice…I note, DHP, that you recently post that, when having taken the days first 300mg of the drug, presumably upon waking, you rapidly note evident positive result, including clarity of thinking…looking back at earlier posts, It strikes me that it took exposure to at least your current daily intake of the full 600mg/day before you noticed your first undeniable positive experience…is that correct? can you confirm /clarify exactly what stage of the trial you first noticed Ambroxol to be working?. I am wondering if you may have felt benefit in outcome as you stepped up through 120-200mg consumption shifts, for example . Thank you for your posting and for getting Amazon on side.

Probably should have kept a daily journal, then I could have traced back my personal observations with more certainty, but I would say yes, it was not until somewhere in months 2-3 at my full daily 600mg that I really became conscious of the brain fog lift, and after that the shoulder pain dissipation, and then some left hand motor improvement in app month 4, which is continuing (as I now notice my keyboard use improvement).

Interestingly found this tonight posted we think from a prior PD Ambroxol trial participant, who if so probably has an NDA and can’t publicly share any more than this quote, but it is quite telling and for me believable: " I was a patient participant on the Royal Free Ambroxol drug trial…if I could afford to, I would continue to take Ambroxol"

https://healthunlocked.com/parkinsonsmovement/posts/137654985/is-anyone-taking-ambroxol-please-share

Also, I’m on Rasagaline, when my neurologist gave me the green light to try Ambroxol he knew that (he put me on it of course), he didn’t mention any compatibility issue there, also did a brief search tonight and couldn’t find anything, not aware of any concern in their interaction (?).

DHP,…yes… I thought, given the number of additional pills and supplements that you are taking…that you might also be on an MAO B-inhibitor, and that is why I raised my comment. I can offer nothing more to the reasoning behind this comment, except I quote from a parkinson’s nurse whom I approached, and she responded …" I have looked into Ambroxol in our drug formulary and it can be dangerous when taken alongside some PD Meds especially Rasagiline, Safinamide, Selegeline. "…:unamused:…worth investigating this with your doctor?

DHP,

I had a feeling that the volume of syrup needed might be the issue, so I if the tablets can be chewed they sound like the better option.
As to flavour, personally I don’t think you can go wrong with lemon or mint.
Thanks for all the information-I shall definitely be giving Ambroxol serious consideration.