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new patent - Trimetazidine, (like a beta blocker?) -dramatical improves fatigue, pain

Discussion in 'General Treatment' started by voner, Nov 14, 2010.

  1. voner

    voner Senior Member

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    this one certainly needs some comments by someone who is following research closely and understands some of the biochemistry (unlike me):

    http://www.faqs.org/patents/app/20100286073

    the Patent cites numerous examples and a small study -- here's a quote describing how the patent author, Paul JENKINS , "discovered" this potential treatment:


    The inventors arrived at the present discovery (forming the basis of the invention) in a completely unexpected fashion. While treating a subject suffering from a cardiac condition with an anti-anginal agent, trimetazidine, the inventors discovered that, within a short time after commencement of treatment, that same subject, also suffering from fibromyalgia syndrome, experienced a surprising and remarkable improvement in all symptoms associated with his fibromyalgia. This effect was later further confirmed in additional clinical studies of fibromyalgia patients for whom currently existing treatments for fibromyalgia had previously been either minimally or completely ineffective.

    [0011]Trimetazidine (1-(2,3,4-trimethyloxybenzyl)piperazine) is a metabolic anti-anginal and anti-ischaemic agent that is used in the treatment of patients with coronary heart disease and stable angina. Unlike the conventional anti-anginal agents, which act by producing haemodynamic changes to restore balance between myocardial oxygen supply and demand, trimetazidine increases cellular tolerance to ischaemia.

    [0012]Trimetazidine is thought to act by inhibiting mitochondrial fatty acid metabolism and secondarily by stimulating glucose metabolism (Kantor, et al., Circ Res, 2000, 86: 580-8). In particular, it has been shown that trimetazidine inhibits the long-chain isoform of an enzyme involved in mitochondrial fatty acid beta-oxidation, 3-ketoacyl coenzyme A thiolase (3KCT), thereby reducing fatty acid oxidation. An associated increase in pyruvate dehydrogenase activity stimulates glucose oxidation. This is thought to be due to the relief of fatty acid-induced inhibition of pyruvate dehydrogenase.

    [0013]Thus, based on the surprising discovery that trimetazidine can be used to treat fibromyalgia and related conditions, the inventors have deduced that any substance that acts in the same manner, i.e. that inhibits fatty acid oxidation and/or stimulates carbohydrate metabolism, should also be effective in treating fibromyalgia and related conditions.



    -- but considering that the DR. Kathy Light of University Utah has published results on benefits of a beta blocker, Propranolol, being beneficial for CFS/FM patients, and Trimetazidine is listed as a "alternative to beta blockers"..... curious..?


    http://eurheartjsupp.oxfordjournals.org/content/3/suppl_O/O12.abstract

    the Patent cites numerous examples and a small study -- here's one example:

    Example 3

    Treatment of Human Subject Diagnosed with Fibromyalgia with Trimetazidine

    [0242]A 32 year old female presented with a 5 year history of complaints of widespread pain--headaches, upper and lower back pain, neck pain, hip pain bilaterally and knee pain bilaterally. General non-specific symptoms were fatigue, symptoms of irritable bowel syndrome (constipation-type), insomnia, morning stiffness and emotional liability.

    [0243]Physical Examination: A physical examination revealed tender points located at: [0244](i) the sub-occipital muscle insertions bilaterally, at the occiput [0245](ii) the medial fat pads of the knees, just proximal to the joint lines, bilaterally [0246](iii) the trapezius muscles, at the midpoint of the upper border of the muscles, bilaterally [0247](iv) the greater trochanter, posterior to the trochanteric prominence, bilaterally [0248](v) the supraspinatus muscles, at the origins, above the spine of the scapula near the medial border, bilaterally.

    [0249]Laboratory Tests: The following laboratory investigations were conducted: CBC, ESR, CRP, Rheumatoid Factor, Thyroid Function Tests, ANA. These tests yielded no positive results. X-Rays were also taken and resulted in no positive findings.

    [0250]Patient History of Prior Treatment: A patient history was taken. Prior treatments targeting pain relief were as follows. OTC analgesics such as paracetamol (also known as acetaminophen), NSAIDs and low dose codeine provided negligible pain relief. Prescription analgesics such as high dose codeine, tramadol and meperidine provided, at best, mild to moderate and very temporary relief and were frequently accompanied by unpleasant side effects. Trigger point injections were refused by the patient.

    [0251]Prior treatments targeting other symptoms included the following. The subject had taken tegaserod for irritable bowel syndrome. Additional prior therapies included zolpidem, midazolam, zopiclone, and chlorpheniramine for insomnia.

    [0252]All of the above therapies were either minimally effective or completely ineffective.

    [0253]Diagnosis: The subject was diagnosed with fibromyalgia syndrome.

    [0254]Treatment Regime: The subject was administered trimetazidine (modified release formulation, Vastarel MR), 35 mg orally, twice daily.

    [0255]Results: Within 24 hours of starting treatment, there was vast improvement in all symptoms and signs of fibromyalgia. Positive results were as follows. The subject reported a "95% reduction" in the widespread pain, with a residual mild headache. The subject additionally reported very significantly increased energy levels, very significantly improved sleep patterns (described as "uninterrupted and very restful"), markedly improved regularity of bowel habits, and very improved mood.

    [0256]Follow-up. After four (4) months of continuous use of trimetazidine (modified release) 35 mg, orally, twice daily, the patient has reported that she continues to experience the same marked improvement in the quality of her life. She has experienced no relapse of symptoms to date.



    A quick search I could find only one other reference (1998) to Trimetazidine in FMS, and none in CFS...

    http://www.jacn.org/cgi/content/full/17/3/300

    here is a quote:
    These complex thiamin abnormalities might explain reduced nitric oxid (and impaired muscle relaxation and microcirculation) or glutathione (and muscle soreness) [6], impaired glycolysis (and muscle fatigue) [5] or even serotonin depletion (and decreased pain threshold) [10] observed in FM.

    Whatsoever, even if excessive alcohol intake is not a FM risk factor, conversely to hypothyroidism or detraining, appropriate metabolic treatment is needed, particularly when blood pyruvate is elevated [5]. Cocarboxylase (IM or sublingual) is markedly more efficient than thiamin alone [11] or magnesium [16] and further studies on other B vitamins (pyridoxal phosphate, riboflavine, folates, thioctic acid), minerals (Mg, manganese, selenium), amino acids (arginine, S-adenosyl methionine, cysteine) or drugs stimulating pyruvate dehydrogenase activity (trimetazidine, carnitine) and phosphorylations (phosphocreatinine, piracetam) are needed [6,10,15].



    //////////////////////////////

    Who is "Paul Jenkins"? The patent lists him as living in England.

    I find this one intriguing. They claim an elimination of fatigue, pain, etc............I guess I suspect another subgroup!

    ........comments? Speculation?
  2. Wonko

    Wonko Senior Member

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    no one else interested in this? no one tried it or on it for something else?

    looks like it might help at least some issues - or make them drastically worse

    I've had some success with treating night sweats, insomnia, some of the pain etc. with beta blockers but the total lack of compromise they cause with all activity was too much for me to handle - even though in theory it's a good thing having a set in stone upper limit to activity (ie they wont let me do anythign but very limited and slow movement) in practice this means nothign ever gets done because the imposed limits are so inflexible

    calcium channel blockers are more flexible on limits but only address background pain in my case

    what I'm tryign to say is I've had lmiited success with medication that affects the heart, but definate success in addressing some symptoms and given these seem to target things like stroke volume, mitochrondrial function etc they seem worth a shot

    unless anyone has tried them and found them to have dire negative consequences?

    edit - eg amongst other things they may help with the aerobic block most pwME have (tho if thats a protective mechanism rather than damage then that could make things a lot worse fast - but I would expect if thats the case then people following several other protocols would know by now), increasing the stroke volume should, as it does for people with corinary issues, help with numerous other symptoms, its claimed to normalise blood sugar and insulin responses etc. etc.

    in short whilst it obviously wont cure ME (just as it wont cure corinary problems only make life a little more bearable for those with them) it looks as if it might increase functionality quite a bit - maybe enough so non essential things can be considered, and TBH it's the first thing I've seen in a few years thats looked like it's worth it to personally spending the money and having a try

    so - opinions, experiences, how much of a muppet am I, etc, are sought
  3. urbantravels

    urbantravels disjecta membra

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    I don't understand what this means. What effect of beta blockers are you talking about?
  4. Wonko

    Wonko Senior Member

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    in order to do anything more demanding than very limited duration low intensity activities most of the time I need to - and here I get a bit wierd - 'overdrive things' - apply more mental force to make my muscles continue working, overcome pain, stiffness, muscle lock (not cramp, muscles affected just go solid and dont want to move at all), disorientation (deal with perceptual distortions and narrowing of awareness which could otherwise stop me in my tracks) - in short a whole host of issues which negatively impact on my ability to do anything at all

    I routinely need to do the same thing to move at anything approaching a normal speed eg walking - beta blockers completely remove my ability to do this - it just doesnt work when I take them - I needed to stop so frequently and for so long that most activities just were'nt practical

    so whilst they cool me down (without them I'm almost constantly too hot but particularly at night) which helps me to sleep and stay asleep thus rest better, help moderate soem types of pain etc. when I use them I essentially cant get anythign done - including bare survival (it's taken me an hour to get to my local shop and back which is under 50m away)

    it's not a trade off I can live with for any length of time given I can function a lot better without them - albeit a lot less comfortably - so I only really use them for occasional pain relief and if I absolutely must sleep and nothign else is working

    I assume the effect is probably adrenaline related and I'm using to much to keep going (as this is my understanding of the function of beta blockers) - which the beta blocker prevents me from doing but more normal adrenal levels definately help some symptoms
  5. Dolphin

    Dolphin Senior Member

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  6. CFS_for_19_years

    CFS_for_19_years Senior Member

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    I think with all the focus on retroviruses this patent application didn't get the attention it deserves. I think at another time it may have gotten more attention.

    I found a link to download the patent application in pdf form:

    http://www.freepatentsonline.com/20100286073.pdf

    This makes it much easier to read, especially the tables summarizing treatment results.

    With regards to "Who is Paul Jenkins", it appears he is an endocrinologist, if I've got the right Paul Jenkins:
    http://www.londonendocrinecentre.co.uk/pjbio.php
    http://www.whri.qmul.ac.uk/staff/Jenkins.html
    http://www.thelondonthyroidclinic.co.uk/about_us/Dr_Paul_Jenkins.aspx

    None of his papers deal with FM/ME/CFS but I suppose an endocrinologist is as well qualified as any doctor to deal with the complexities.

    I printed the PDF for my own use and to show my PCP later today. Trimetazidine is not available in the US but it is available in most other countries. I would have to ask my doctor to write a prescription that I could get filled by mailing it to Canada. One day's supply is about one dollar, using the dose of 35mg twice a day, stated in the patent application.

    The PDF has some useful information wedged between a lot of unreadable nonsense. If you have printed the PDF, here is where I found useful information:
    Page 2, Summary of the Invention [0010]
    Page 8, Method of Treatment-Overview [0116] and [0117]
    Page 14, Dosages and Measurable Result [0182] to [0189]
    Page 15, Examples, Example 1, Treatment of Human Subject...[0211] to [0226]
    Page 16, Example 2, Treatment of Human Subject...[0227] to [0241]
    Page 17, Example 3, Treatment of Human Subject...[0242] to [0256]
    Page 17, Example 4, Treatment of 8 Human Subjects [0257]. A table summarizing the results of 8 subjects follows. If you don't want to wade through a lot of reading then this table is a good summary.
  7. FunkOdyssey

    FunkOdyssey Senior Member

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    I'd like to hear from people who've tried it. We need some guinea pigs.
  8. CFS_for_19_years

    CFS_for_19_years Senior Member

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    I may be the first guinea pig to report back, but it will take a few weeks just to get the trimetazidine. It's not stocked in the US. Here's an article about why the FDA hasn't approved it yet:
    http://www.theheart.org/article/735451.do

    and here are some adverse events:
    http://www.ncbi.nlm.nih.gov/pubmed/16268443

    Note, this was a retrospective study of neurologic patients, not the general population. The parkinsonism was reversible, i.e. it disappeared when the drug was withdrawn.
  9. Cort

    Cort Phoenix Rising Founder

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    I know someone who;s taking proponalol for I guess its anxiety - for it's calming effect. She figured out why it might help and then she tried - I think she bought it from overseas - its now a part of her protocol...
  10. CFS_for_19_years

    CFS_for_19_years Senior Member

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    While surfing the web trying to find out more I came across the same protocol with a different patent application number, same text:
    http://www.freepatentsonline.com/20100022551.pdf

    ??? I'm perplexed! There are different inventors listed, different country, different time frame.

    My PCP is sending me to my rheumy to discuss trimetazidine. I don't hold out much hope for getting an rx. I belong to an HMO that only uses protocols that have been proven by double-blind placebo controlled studies. (Don't get me started on that B**S**!)

    I've been sick for 20 years now.

    Ordering trimetazidine from offshore pharmacy without prescription = no bid deal

    Getting my health back = priceless

    If anyone else would like to step up to be a guinea pig, I can provide links to offshore pharmacies. (To mod: let me know if that is a no-no.) Using the protocol, the cost is one dollar per day.

    There is a website called drugbuyers.com that is helpful to check when using US/Canadian/International pharmacies. I would give them a look before ordering from an unknown pharmacy.
  11. CFS_for_19_years

    CFS_for_19_years Senior Member

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    I bit the bullet and ordered a small supply from an offshore pharmacy. It may take 10-14 days to get here. I'll post my results, good or bad.
  12. valentinelynx

    valentinelynx Senior Member

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    Trimetazidine: a thought or part of one

    First, I'm not an expert. Never heard of this drug before, but looked it up.

    Re: beta blockers, such as propranolol... Trimetazidine is not a beta blocker and does not work the same way as a beta blocker, so one shouldn't draw conclusions about how good Trimetazidine would be based on a response to a beta blocker. The reference to it being an alternative to beta blockers is due to both drugs being used to decrease ischemia in the heart. Beta blockers do this by decreasing the amount of work the heart muscle does. Trimetazidine appears to do this by making sure that ATP is available to fuel the heart, although there appears to be some controversy about how it actually works.

    Theoretically, it sounds plausible that Trimetazidine might help with FMS or CFS or both. Love to hear people's experiences.
  13. CFS_for_19_years

    CFS_for_19_years Senior Member

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    valentinelynx,

    Thank you for your explanation. I'm somewhat cognitively impaired, depending on what day it is, so I'm glad you were able to write this!

    To repeat, trimetazidine is not a beta-blocker, it is a metabolic modulator. Here is an article called Metabolic Modulators for Chronic Cardiac Ischemia

    http://www.bioenergy.com/pdf/mf/sl/...bolic modulators chronic cardiac ischemia.pdf

    I'm expecting my order of trimetazidine to arrive in a few days. I should know within 72 hours of taking it whether it will do me any good.

    If I continue taking it I will certainly let my doctors know. Since it is not available in the US I doubt if many US doctors will have experience with it. If my primary doc gets uneasy, I will ask him to refer me to cardiology for continued care. I would prefer to get an rx from a doctor who is seeing me, rather than one I've never met. But I do what I have to, as I'm sure many here do.
  14. orion

    orion Senior Member

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    Hi CFS_for_19_years,

    I'm considering trying Trimetazidine. Can you give me details of which offshore pharmacy you used.

    Thanks
  15. CFS_for_19_years

    CFS_for_19_years Senior Member

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    orion,

    Here is the pharmacy I used because I could get a small amount of trimetazidine:
    http://www.bmpharmacy.com/product_info.php?ref=250&products_id=126
    Scroll down to the middle of the page. You'll see you can get 60 tablets for $32.50.
    Edited to add: DO NOT USE BM PHARMACY.
    A member of our forum, Hip, found this post about BM Pharmacy:
    http://www.edguider.com/forum/scammer-pharmacies/674-warning-about-bm-pharmacy-read.html
    Thank you Hip for finding this post and letting us know about it.


    I haven't received this prescription yet so I have no idea where it's being filled. If you use this pharmacy, just to be on the safe side, find out if your credit card company can issue you a throw-away credit card number for this one purchase. Bank of America can do that. About two years ago, there were problems with unauthorized charges to credit cards when people used this pharmacy.

    If trimetazidine works for me, I will go with one of the pharmacies listed below because they have good reputations as listed on www.drugbuyers.com.

    Drugbuyers.com also has discount codes for some of these pharmacies too, like 10% off:
    http://www.rx2world.com/Products2.asp?Brand=Carvidon MR (Vastarel MR, Generic Trimetazidine)&T=a

    http://www.healthpluspharmacy.com/P...n MR (Vastarel MR, Generic Trimetazidine)&T=a

    http://www.freedom-pharmacy.com/Pro...n MR (Vastarel MR, Generic Trimetazidine)&T=a

    All the pages look alike, don't they? I haven't figured out the connection any of them have to one another. They're using the same script to build their web pages anyway.

    If you're NOT based in the US you may find other pharmacies to your liking. I'm in the US.

    As soon as I have my Rx I'll post in the forum. Btw, there is a very short medical history to fill out. I listed my chronic illnesses as chronic fatigue syndrome and fibromyalgia. It took the pharmacy two days to approve the order. It was shipped on Dec 21 so maybe it will be here by the end of the week.

    Best wishes
  16. CFS_for_19_years

    CFS_for_19_years Senior Member

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  17. CFS_for_19_years

    CFS_for_19_years Senior Member

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    My order of trimetazidine arrived today.
    Purchase date was Dec. 19th.
    It originated from Mumbai India on December 24th.
    Tablets are in a blister pack that says Trivedon-20 (brand name).
    Manufactured by Cipla, Ltd. July 2010, expire July 2013
    Cost for 60 20mg tablets $32.50 including shipping

    I'm NOT going to take these for TEN more days. I'm taking an antibiotic, Cipro, and don't want to begin a new medication because I won't know if any side effects will be from the Cipro or trimetazidine. As much as I'd like to be a guinea pig, I'm still going to be cautious about some things!
  18. SpecialK82

    SpecialK82 Senior Member

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    good idea 19 years, better to keep the two seperate. Thanks for letting us know the status, I am excited to hear the results of your trial -fingers crossed for you.
  19. orion

    orion Senior Member

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    CFS_for_19_years,

    Thanks for the warning about BM Pharmacy.

    I evetually chose to order some Trimetazidine from www.drugspro.org as I've used them before. I was already going to buy some Cycloferon from them and noticed that they sold Trimetazidine as well. So I ordered both drugs together. However, I won't be taking any Trimetazidine until I'm sure whether or not the Cycloferon is working.
  20. CFS_for_19_years

    CFS_for_19_years Senior Member

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    I took Trimetazidine for about a week at the dose of 20 mg three times a day. I didn't notice anything. No improvement, no side effects. I have stopped taking it.

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