NIMODIPINE use in M.E. / CFS : A comprehensive guide. S. Parker (MBA, BSc) January 2014

pattismith

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S-VV

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I use Nimodipine. It gives a noticeable cognitive benefit.

I wonder how many more treatments like this are buried in the web...
 

pattismith

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One pathway that could explain the positive effect of Nimodipine on ME/CFS is the nucleotide transporter inhibition.

"Among the dihydropyridines tested, nimodipine proved to be the most potent inhibitor of hENT-1, ..., whereas nifedipine, nicardipine, nitrendipine, and felodipine exhibited 100-fold less effective inhibitory activity. Nifedipine, nitrendipine, and nimodipine inhibited hENT-2 ....; however, nicardipine and felodipine had no significant effect on hENT-2"

One of the nucleotide transported is adenosine, which means that Nimodipine is an ADENOSINE REUPTAKE INHIBITOR, so it increases blood adenosine level and activation of adenosine receptors.

On the other hand, some L Calcium channel blockers have inhibition effect on some adenosine receptors, mainly A1 and A3 receptors.


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"Pyridine derivatives, when bearing a 4-alkyl but not a 4-phenyl group, maintained affinity for adenosine receptors. These findings indicate that the dihydropyridines may provide leads for the development of novel, selective A3 adenosine antagonists."

This means that Nimodipine may enhance A2 receptors activity and decrease A1 and A3, which is exactely what we need, because A1 lower cAMP and A2 increases cAMP.

"All adenosine receptor subtypes (A1, A2A, A2B, and A3) are G-protein-coupled receptors.
The four receptor subtypes are further classified based on their ability to either stimulate or inhibit adenylate cyclase activity.
The A1 receptors couple to Gi/o and decreases cAMP levels, while the A2 adenosine receptors couple to Gs, which stimulates adenylate cyclase activity.
In addition, A1 receptors couple to Go, which has been reported to mediate adenosine inhibition of Ca2+ conductance, whereas A2B and A3 receptors also couple to Gq and stimulate phospholipase activity."
" Activation of A2A receptors produces a constellation of responses that in general can be classified as anti-inflammatory"


EDIT: about Mast cell degranulation for those that are concerned by this issue:


." In different animal models A1, A2b and A3 adenosine receptor subclasses have all been implicated in inducing bronchospasm. whilst occupation of the A2a receptor generally has no, or the opposite effect"

so this explains why Nimodipine might not having much bad effect on mast cells degranulation, as it may produce an indirect activation of A2 receptors, and inhibition of A1 and A3
 
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Dechi

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I’ve been using it for a few years. At first I was taking higher doses but this is very expensive and after a while I just went down to a small maintenance dose.
 

pattismith

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@Gingergrrl

This is a 2019 study, it makes a link between beta 2 adrenergic receptor and L type VGCC

"The beta 2 adrenergic receptor (b2AR) has been identified as a potential mediator for this - a receptor that our lab has shown tightly regulates the activity of the L-type voltage-gated calcium channel 1.2 (Cav1.2).
Together these results support our hypothesis by showing that bA42 acts through b2AR to partially upregulate Cav1.2 activities in neurons and that such upregulation can be inhibited by blocking b2AR. Future work will exemplify this upregulation mechanism by examining its contributions to cytotoxicity and AMPAR expression."

"Gated Calcium Channel 1.2 through the Beta-2 Adrenergic Receptor"
 

Gingergrrl

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@Gingergrrl This is a 2019 study, it makes a link between beta 2 adrenergic receptor and L type VGCC
I'm sorry I was so late to see your tag @pattismith. I am horrible at understanding scientific studies but is there a connection between the beta adrenergic autoantibodies and the L type VGCC or only between the receptor and the L type VGCC? As far as I know, there is no commercial test for the L type autoantibodies and only for the N type and P/Q type. What does this study mean (in very basic terms :nerd:)?
 

pattismith

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I'm sorry I was so late to see your tag @pattismith. I am horrible at understanding scientific studies but is there a connection between the beta adrenergic autoantibodies and the L type VGCC or only between the receptor and the L type VGCC? As far as I know, there is no commercial test for the L type autoantibodies and only for the N type and P/Q type. What does this study mean (in very basic terms :nerd:)?
this makes a connection between POTS study that found antibodies activating the beta 2 adrenergic receptors, which means that L type VGCC are also activated in POTS, as a consequence of beta2 AR activation.
So this could explain at less partly why Nimodipine (L VGCC blocker) could have some effect for people with some kind of dysautonomia, especially when beta 2 AR are pathologically activated.

Not sure if I am clear!
Hip made some explanations about autoantibodies in POTS here
 

Gingergrrl

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this makes a connection between POTS study that found antibodies activating the beta 2 adrenergic receptors, which means that L type VGCC are also activated in POTS
Do you know if there is a commercial test (outside of research studies) for autoantibodies of the L-type calcium channel (VGCC)? I have been trying to figure this out for several years b/c I have autoantibodies against the N-type but not against the P/Q type (on tests from Mayo & Quest). But I have not found any lab that tests the L-type and I am so curious b/c certain meds and anesthesias involve the L-type and I do not know if they would affect me without knowing if I have the autoantibodies.
 

mitoMAN

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Very interesting. I have Beta 2 Receptor Autoantibodies and just stumbled across this thread.
Will give it a try!

From what I see this could be combined with low dose Propranolol to further block the Beta 2 AR Activation?

this makes a connection between POTS study that found antibodies activating the beta 2 adrenergic receptors, which means that L type VGCC are also activated in POTS, as a consequence of beta2 AR activation.
So this could explain at less partly why Nimodipine (L VGCC blocker) could have some effect for people with some kind of dysautonomia, especially when beta 2 AR are pathologically activated.
 
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For those who want to try NIMODIPINE, (a L voltage gated calcium channel blocker, vasodilatator and neuroprotective drug), and who need a document to bring to their doctor.
I wonder- why am I so late to even know that this exists? I should definately be trying this but apparently have not spent enough time yet here in PR to know it existed.
 

godlovesatrier

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@Hip Is this mentioned in your recovery thread? There are quite a few patient recovery stories within the pdf mentioned above, but I just read this one:

My previous health: My immune system problems became evident in 1983 when I developed Multiple Chemical Sensitivity. M.E. came on suddenly, in 1991 when I was 34 years of age, about 6 weeks following a heavy flu. I was housebound and so fatigued that I was sleeping most of the day and night, and suffering from a broad range of M.E. symptoms.

Other treatments that I tried: Medical tests and advice have pointed me to a variety of treatments that have reduced my symptoms. Magnesium sulphate injections halted my decline; high doses of evening primrose oil for three months eliminated the twitching and "burning" in my limbs; undertaking an elimination diet to discover foods to which I was intolerant and then avoiding them cut out the chills, dizziness, swollen glands, a lot of the brain NIMODIPINE USE IN M.E. / CFS: A Comprehensive Guide Page 16 (Moral rights asserted by Susan Parker, 2013.) fog, the constant heavy fatigue, and the brain-too-busy-to-sleep nights. I subsequently felt bright in the mornings but was still quite fatigued by any activity and needed a nap in the afternoon. As my DHEA barely registered on tests and the adrenal curve was abnormal, I took DHEA supplements for 2 years. This resolved my orthostatic intolerance (brief drop in blood pressure upon standing) and slightly increased my energy and stamina. A course of tropisetron (Navoban) gave me a boost in functioning (but the expense to benefit ratio was high so I didn't repeat it despite my doctor’s encouragement). Seven years of dietary advice and supplements, homeopathic treatments, and enzyme potentiated desensitization (EPD, an allergy treatment) from the Royal London Hospital for Integrated Medicine improved my nutrition, fitness and resilience. (Notes: 14, 18, 31, 87, 89, 125.)

20% of well before nimodipine: Despite the improvements, I was largely housebound, going out occasionally on foot for short distances or on longer outings in a wheelchair. I needed a long nap every afternoon and a day or more of rest after an outing. I had a lot of muscle pain after a morning of light household tasks. I was about 20 to 25% of well. I have listed these previous therapies to show the degree of improvement that I had before I used nimodipine. If I had tried it earlier I would not have evidenced much success as the benefit would have been masked by my food intolerance symptoms. It is also possible that the earlier treatments put my body's systems in a state where it could benefit from the increased blood flow to the brain and its knock-on effects of nimodipine.

30% of well on 45 mg nimodipine: At this point in 2006 my doctor thought that due to my otherwise poor quality of life, I should be allowed to take the unknown risk of using an untested drug. After researching the drug, I began taking nimodipine. I started on 15 mg (1/2 tablet) and increased the dose by 15 mg every two weeks. I didn’t have any side effects, tolerating it well although I have a history of intolerance to some types of drugs. On the 4 th day of taking 45 mg per day, I got a sudden rush of foul-smelling odour in my arm pits and felt nauseous. The 5th day was the beginning of my improvement. I was notably better and the previous day's symptoms had subsided. I no longer felt sleepy the whole of the night so stopped sleeping in the afternoon, but I did need an hour of rest in a chair. At this dosage I couldn't do more outside of the house, but I was more active inside the house. I was about 30% of well.

55% of well on 75 mg of nimodipine: After two weeks I increased the dose to 60 mg per day and again got the odour and nausea on the 4th day, and then improved on the 5 th day. At this point I didn't need an afternoon rest, and I could walk further and go out for a whole day. My muscle soreness, joint stiffness, cold extremities, and brain limitations were reduced. After a year at 60 mg, I increased the dosage to 75 mg per day split between morning, noon, and late afternoon. I could do much more at this level, having improved in strength and ability and I was slowly reconditioning my mind and body. I was very busy in the home and could go out most days to do a little shopping. I participated in volunteer and social activities and enjoyed long day trips and holidays overseas. I could walk 3 miles a day. With the use of pacing to vary activities throughout the day and across days, I was functioning at about 55% of well. In the same month that I increased dosage to 75 mg I also began injections every six months of 300,000 units of Ergocalciferol Vitamin D which would have boosted the general health of my body.

80% to 90% of well on 90 mg of nimodipine: In 2008 I increased the dosage to my present level of 90 mg per day, taken as 30 mg three times a day. I saw a gradual increase in benefit such that I now organise and manage large projects and studies using intensive as well as repetitive mental and physical activity. I can now walk 6 miles a day, run and dance, and NIMODIPINE USE IN M.E. / CFS: A Comprehensive Guide Page 17 (Moral rights asserted by Susan Parker, 2013.) drive a car at home and abroad. In 2010 I was 70% of well and now, in 2013, I am about 80% of well with mental clarity nearing 90%. Much reduced but still a problem is face pain from continuous concentration, and neck cramp causing vertigo and nausea from carrying an item of moderate weight. Trials at reducing the dosage: I have tapered down my dosage of the drug 5 times, but saw a progressive regression with each 15 mg reduction. I lost all benefit when I reduced to a dosage below 45 mg (which is the level at which I first felt a benefit.) After each reduction trial I have tapered the dose back up to the starting level.

My present health: I have now been taking nimodipine for more than 7 years and have never had any side effects other than the fleeting ones on the 4th day following a dose increase. My blood pressure has always been the low-end-of-normal; it hasn’t been changed by the nimodipine use and doesn’t cause dizziness. I have regular blood screenings and have two “abnormal” results. My serum ferritin has occasionally been high, but that pre-dated the nimodipine use. My liver ALT enzyme varies from 30 to 84 (reference range of 10 to 35) and this is possibly caused by the nimodipine (2% get this effect), but it is a transient effect common with many medications and does not mean that the liver is harmed; my normal blood counts confirm this. (Notes: 10, 13.) I continue various homeopathic remedies, and have regular vitamin D injections because I don’t tolerate oral supplements. Although many of my intolerances have disappeared over the years, I still need Creon digestive enzymes to digest meat and fish, and I am still intolerant to herbs, spices, flavourings, onions, citrus, eggs, beef, apples, peppers, mustard, and a few other things. I have every reason to think that I will continue to make progress.
Patient goes on to say he's taken it for 7 years at a dose of about 90mg a day in 3 split doses and has been able to return to most activities but still has a few symptoms, can exercise, tolerate intense cognitive jobs (would love a boost like this in my current job as my brain just cannot process information at a decent pace anymore).
 

Hip

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@Hip Is this mentioned in your recovery thread?
Nimodipine has not so far been included in mentioned in the ME/CFS Recovery and Improvement Stories thread, because I never found any good nimodipine recovery stories. But this is a great story, so I have just added it to the thread. Thanks for posting it.

Where was this story originally posted? In a private Facebook group perhaps?
 

godlovesatrier

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Hi Hip,

Yes it does stand out doesn't it. The patient seems to be called Susan Parker. My guess is the pdf it's in is probably from some sort of group. Not too sure which one which is annoying. It was taken from a pdf on theactionforme website. Author of the pdf is Susan Parker MBA, Bsc.

Yes I've just reread it. Susan Parker is the patient. Group appears to be 25megroup.org (25% ME Group)

It's got her email address on the pdf as well. 2014 was the date.

Pdf link is attached at the top of this threads page. Just spotted it.
 

Dechi

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@godlovesatrier I spoke to Susan Parker a few years ago. In 2017 I think, a little while after I started taking Nimodipine. She was still taking it and doing well.

By the way thanks to this thread I’m back on nimodipine. First dose tonight, I’m starting slowly at 8,75 mg.
 
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That's great, thanks @Dechi Sadly over the last 2 years I've realised I also have a histamine problem. I can't see how lack of blood flow to the brain or limbic system dysfunction as per Dr Kristina Orr would effect the histamine release from h2. Would be lovely if it did though. I lived in the city until 2020 - and that was the year I moved out, also the year my pollen allergy went wild. As soon as tree pollen season kicks in I struggle for about 2 months now before it gets better, this used to be 2 weeks in the city!!

Going to try pepsid and doxepin though, the latter seems better. But I was hoping nimodipine might resolve a root cause issue. Sadly I am coming to realise that I think my mother has undiagnosed MCAS as she has half the symptoms of MCAS but with no generalised immune dysfunction. She takes Allegra.