Nimodopine - very interesting. Anyone have experieince with it or know about it?

Was doing a bit of research and came across this:

Nimodipine

Nimodipine (marketed by Bayer as Nimotop) is a dihydropyridine calcium channel blocker originally developed for the treatment of high blood pressure.
Nimodipine (Wikipedia)

Nimodipine is a calcium channel blocker.
It works by normalising the blood circulation in the brain, especially through the smallest blood vessels.

It also works by relieving areas of localised vessel spasm in the brain decreasing the vascular headaches sometimes associated with ME-CFIDS

In ME-CFIDS there can be reduced blood pressure due to the neurally mediated hypotension found in many patients.

Neurally mediated hypotension is where the blood drains from the head causing parts of the brain to have inadequate circulation.
This is why brain fog often occurs.



The re-stabilisation of the brain circulation releases the neurotoxins, which have become trapped in the brain in a controlled fashion.
Restoring the circulation to the brain and to the pituitary gland allows hormones to reach various glands in the body.
This enables the bodys distribution system to work as intended, which is vital in order to take oxygen, nutrients and any medication where it is needed. This is analogous to clearing blockages from a railway track to allow the trains to operate again.
Dr. David Mason Brown

Dr. Goldstein also recommends it.



Also, this:

A Book Summary by Dr J A Skerkey - Betrayal By The Brain









(full text available from Amazon.com and Amazon.co.uk.)





I am a family physician who developed CFS in October 1993. Naturally since then I have become very interested in this illness and have been doing extensive reading on the topic.



The first book I found that made sense of this disorder was Dr. Jay Goldsteins 1993 book, CHRONIC FATIGUE SYNDROMES: THE LIMBIC HYPOTHESIS. In this book Dr. Goldstein offers a neurological explanation for the myriad of bizarre symptoms one sees in Chronic Fatigue Syndrome and suggests treatments that often work. I began to use his treatment protocol on myself, without success, and on my CFS patients, often with dramatic success.



In March 1996 I spent a week in his clinic in Anaheim Hills, California seeing patients with him and trying several more of the medications myself. Again I saw dramatic successes in patients, but so far nothing has worked for me.



Dr. Goldstein has now published a new book entitled, BETRAYAL BY THE BRAIN: THE NEUROLOGICAL BASIS OF CHRONIC FATIGUE SYNDROME, FIBROMYALGIA SYNDROME AND RELATED NEURAL NETWORK DISORDERS. In my opinion this book is even better than his 1993 book and I will attempt to give you a very brief synopsis.



After ruling out the many illnesses that can cause fatigue, many physicians will tell their CFS patients that their symptoms are " psychosomatic". Well, there is overwhelming evidence that CFS/FMS symptoms are "neurosomatic", and not psychosomatic; that is to say that CFS/FMS is a NEUROLOGICAL ILLNESS. It is a neurotransmitter/receptor dysfunction problem. The symptoms occur because sensory information is not properly managed by the brain.



The basic problem starts with the prefrontal cortex of the brain. The PFC receives sensory information from the environment, both the external and the internal environment. It does not interpret the information. Rather, it assigns a weight to each signal according it relative importance, i.e. the PFC attaches the proper relevance to the incoming signal. This process is called gating.



Gating is abnormal in CFS/FMS and information that should be given low relevance is often instead given high relevance. In order to understand this, you must familiarize yourself with a crucial concept called signal to noise ratio. Your prefrontal cortex is



supposed to assign a high relevance to the signal and low relevance to any other sensory information. For example, the signal at the moment is your concentration on what you are now reading. Everything else is "noise". The television may be on in the other room--your PFC is supposed to assign that low relevance. The room may be a bit too cool--low relevance. There may be a fan running, again low relevance. The person next to you may be wearing perfume--so what! Instead, if your prefrontal cortex assigns all of these distractions high relevance, your concentration falters, or you may become overwhelmingly fatigued as you try to increase your concentration etc.



Abnormal gating makes walking a city block feel like youve walked ten miles; may make supposedly normal odors seem like you are awash in a sea of noxious chemicals; make you feel pain inappropriately; you may become worse when concentrating on the road at night, or experience a panic attack when you go to the mall, etc., etc.



Gating information is transmitted to your thalamus by a neurotransmitter called glutamate. Glutamate levels are abnormal in the CFS/FMS brain. Norepinephrine, a neurotransmitter that increases signal to noise ratio is low in the CFS/FMS brain, whereas substance P, a neurotransmitter which lowers signal to noise ratio is increased in the CFS/FMS brain. (Injection of substance P into the cerebrospinal fluid of healthy volunteers gives them diffuse body pain similar to that seen in FMS.)



So, the thalamus receives all this misinformation and has to modulate signals and transmit the message to various other brain centers. The thalamus is crucial to normal brain functioning. It modulates signals that control such things as pain information, appetite, mood, sleep, autonomic nervous system, libido, and the neuroimmunendocrine system. All these are abnormal in chronic fatigue/ fibromyalgia syndrome.











There are four influences on how and why an individual will get CFS/FMS.



1) Genetic susceptibility. This tendency can be strong or weak or anything in between. If it is strong, a person will develop a neurosomatic illness no matter what, often beginning in childhood. Otherwise, expression of the trait is influenced by other factors i.e., childhood abuse, viral infections, anesthetics, pronounced physical or emotional stress, childbirth, trauma. There is an increased family history of panic disorder. There is often a history of psoriasis, allergies or asthma, sleep disturbances, irritable bowel syndrome, premenstrual syndrome, bruxism, or tinnitis.



2) Developmental issues. While toddlers brains are still developing and forming neural network connections, it is important that the child be in a safe nurturing environment. If a child feels unsafe for a period of time from birth to puberty, his brain learns to be hypervigilant and to interpret the saliency of sensory input differently than a child who feels secure i.e., their brains learn to attach increased relevance to incoming stimuli instead of ignoring irrelevant stimuli. The prefrontal cortex, which gates sensory input according to its saliency every millisecond, must learn what is salient over time and integrate those experiences and attitudes with a genetic developmental predisposition.



This also leads to elevated levels of substance P, enabling him to attend to a wide range of stimuli, as well as transiently elevated cortisol levels with consequent downregulation of the HPA axis. Central norepinephrine levels are low, contributing to dysautonomia.



3)Viral infections. Viruses can produce persistent or hit & run infections which could alter neuronal transport as well as production of neurotransmitters in a genetically predisposed individual. More than one virus may be involved. Two viruses may interact with each other and enhance virulence. Viral gene products and host gene products may interact as well. Flu-like illnesses are known to deplete brain norepinephrine. Cognitive dysfunction in CFS/FMS may be caused by a similar mechanism as the gp120 glycoprotein in AIDS causes dementia.



4)Environmental triggers. The influence of genetic, developmental and/or viral factors results in impaired flexibility of the brain to alter the function of its neural networks to deal with changing internal or external circumstances i.e., a reduction in neural plasticity, a decreased ability to re-regulate the brains response to stimuli. The synaptic density of neurons fluctuates depending on circulating levels of various neurotransmitters and hormones. In CFS there is decreased neural plasticity, therefore various stimuli (smells, increased concentration, exertion, shopping malls) make the individual sick.



SPECT scans show anterolateral and dorsolateral hypoperfusion, the right hemisphere worse than the left. The right hemisphere deals mostly with novel situations and uses norepinephrine. Norepinephrine is crucial to cognitive novelty. The left hemisphere deals mostly with repetitive, well-routined, pre-learned activities and uses mainly dopamine. Dopamine is critical to cognitive routinization. Flu-like illnesses are known to deplete brain norepinephrine.



Regional cerebral blood flow is consistantly found to decrease after exercise or any activity that makes the patient worse, for example doing calculations.



PET scans show activation of the dorsolateral prefrontal cortex along with decreased regional cerebral blood flow to the left angular gyrus, part of the neural network involved with tasks that require "willed action". Hypoperfusion and malfunctioning of the inferior parietal cortex leads to inappropriate sensations, behavior and emotions.



All stressors that require norepinephrine where the patient cannot produce enough, make the patient worse. If an individual is on the fence of norepinephrine signal to noise control and gets a flu, there is depletion of brain norepinephrine and the patient



can develop CFS/FMS if she/he is genetically programmed to have increased substance P, for example.



OK, lets discuss the various symptoms one sees in CFS. Lets start with PAIN.



The nucleus in the thalamus that deals with pain has two pathways coming into it, a pain pathway and a touch pathway. But they share a single pathway from the thalamus to the cerebral cortex, where the message is interpreted. When pain occurs, the touch pathway is inhibited by thalamic GABA production. Impairment of this GABA secretion would result in touch sensation being perceived by the cortex as pain, or in inappropriate pain interpretation (FMS).











Stimulation of the thalamus by electrodes in awake subjects causes them to experience pain they had years ago, a recurrence of pain in old scars etc. CFS patients experience this and complain of recurrence of pain and odd bodily sensations when the fatigue gets worse.



The basal ganglia neurons encode pain INTENSITY but NOT the LOCATION. Therefore, the basal ganglia are likely involved with a diffuse central pain disorder like FMS.



Case History: A 45 yr old immunologist with familial Parkinsons disease, right side far worse than left, since age 38, developed CFS/FMS. A stereotactic left pallidotomy was performed. (The patient is awake during this procedure.) As soon as the left globus pallidus was cut the right-sided dyskinesia markedly decreased, and his right-sided fibromyalgia pain was reduced by 75%.



In summary then, dysfunctional sensory processing leads to inappropriate responses to a given stimulus. So, a patient may feel burning pain or severe weakness for no apparent reason, perspire profusely when he is not hot, or gain 30 lb in 6 weeks without changing eating habits.



The dorsolateral prefrontal cortex controls mood, organization, planning activities that require sequential tasks, motivation and drive, self-analysis. It is also involved in the making of new memories.



MEMORY: The prefrontal cortex regulates the hippocampus in new memory production. With prefrontal cortical dysfunction, situations are erroneously interpreted as novel i.e., that there is no cognitive repertoire for it. This leads to anxiety and other inappropriate responses.











Memory production occurs if post-synaptic neurons increase secretion of nitric oxide. Nitric oxide diffuses into the pre-synaptic neuron and increases glutamate production which strengthens the synaptic connection. If there is not enough nitric oxide, or enough glutamate, the individual cannot strengthen that synapse to make a new memory.



Since nitric oxide is anxiolytic, a decrease in nitric oxide leads to an increase in anxiety. Nitric oxide increases serotonin and norepinephrine and dopamine. If nitric oxide is low then dopamine is Iow, leading to fatigue, behavioral changes, decreased attention and decreased cognition.



SLEEP: Short-term memories are made in the hippocampus and are strengthened by repetitive hippocampal neural firing during slow-wave delta sleep. REM sleep is also vital for consolidation of new memories. THESE ARE BOTH DYSFUNCTIONAL IN CFS/FMS.



The reticular nucleus of the thalamus, via GABA inhibition, controls the transition from awake to sleep. Impairment here would impair sleep onset and sleep maintenance.



The cortex and the reticular nucleus also play a major role in the production of delta sleep. This is dysfunctional in CFS. Slow wave sleep is necessary to restore neuron glycogen stores that are progressively depleted during waking.



Substance P (which is increased in CFS) causes the release of excitatory neurotransmitters. This can lead to nightsweats, bruxism, nocturnal panic attacks, and nightmares.



The reticular formation in the brainstem projects to the thalamus and also projects to the hypothalamus and the cerebral cortex. Dysfunction here can cause insomnia. Sleep is a very complex phenomenon.



No one brain structure is uniquely involved with the control of a single sleep or waking state. Different densities of sleep or wake-active cells occur in each region.



Many neurochemicals are involved in sleep control; serotonin, GABA, adenosine, prostaglandins, insulin and many more.



EXERCISE: Exercise should cause an increase in norepinephrine, cortisol, B-endorphins, growth hormone, certain interleukins, adrenaline and noradrenaline, temperature, and regional cerebral blood flow, but doesnt in CFS/FMS.



High levels of Substance P have repeatedly been found in CFS and may be responsible for the inappropriate post-exertional fatigue.



Exercise-induced temperature elevation is NOT the result of heat generated by increased activity, but is neurohormonally mediated. Similar mechanisms may be responsible for the temperature intolerance commonly experienced by CFS patients and in the often low basal body temperatures seen.



CHEMICAL SENSITIVITIES: Chemical sensitivities is a decreased signal to noise ratio phenomenon. Low level exposure to previously well tolerated foods and smells now make the patient sick. Olfactory information goes directly into the thalamus, which, as you already know by now, is dysfunctional!



FATIGUE: Fatigue is caused by dysfunctioning thalamic areas. In the 1930s Dr. Wilder Penfield, working at The Montreal Neurological Institute, used direct electrode stimulation of various brain sites in wide-awake volunteers. Stimulation of one site would elicit a clear memory of a long ago event; of another site, perhaps the distinct odor of cooking, or the sound of a telephone ringing etc., etc. Some of the subjects, when being stimulated in the medial temporal lobe, reported a sudden onset of severe fatigue, "like someone turned on a faucet and drained all the energy out of me."



Dysfunction of the AUTONOMIC NERVOUS SYSTEM is manifested by low blood pressure and orthostatic hypotension, or, what is now being called neurally mediated hypotension (you dont need a tilt table test to show this!), Reynauds phenomenon, rapid heart rate, temperature dysregulation, & weird skin sensations.



COGNITIVE & LANGUAGE TASKS: PET scans done while the subject is doing problem solving, calculations, explanations etc., show the neodentate lobe of the CEREBELLUM is involved in these tasks.











These areas are involved in the process of word finding. (often a problem in CFS/FM). The neodentate of the cerebellum acts as a computer to control prefrontal cortical symbolic representations of information, ideas and concepts, and is involved in carrying out such operations as: counting, timing, sequencing, predicting and anticipatory planning, error-detecting and correction, shifting of attention, pattern generation, adaptation and learning. Many of these abilities are impaired in CFS/FMS.



Waxing and waning of symptoms may be related to variable production of compensatory factors such as thyrotropin releasing hormone, corticotropin releasing hormone, nitric oxide, GABA or one of the subunits of the GABA receptor.



TREATMENT - Treatment is directed towards correcting a central deficiency of norepinephrine, nitric oxide, oxytocin (co-exists in the same cells that release CRH), Neuropeptide Y, etc.



Most of the medications on the protocol list work quickly and many patients who have been sick for years can show dramatic improvements within thirty to forty minutes after taking an effective medication. These medications have a good safety profile and Dr. Goldstein claims a 95% treatment success rate, meaning significant improvement in 95% of patients.



In my own practice, my success rate is approximately 50%, but that is because there are a few agents on the list that are not available in Canada, and a few, that I, so far, will not use.



Some of my patients have responded with an 80% plus improvement in symptoms to a single agent and have returned to work after absences of eight or more years. Most who respond, however, require two or three medications to achieve this level of improvement. For example, one of my patients, a 48 year old engineer who had been unable to work for eight years because of severe fatigue, severe fibromyalgia pain and severe cognitive dysfunction responded immediately 30 minutes after I gave her a 30mg capsule of nimodipine with about a 50% amelioration of her cognitive dysfunction. She had not been able to read so much as a magazine article for the past 8 years because by the time she got to the fifth line, she would lose the context. When I called her in from the waiting room 40 minutes after she had taken the medication, she had a big smile on her face and said she had been reading Newsweek in the waiting room and could tell me the content of the article. The nimodipine had done nothing, however, for her other symptoms. I sent her home on 30mg three times a day. Two weeks later I increased the dose to 60mg three times a day. She estimated that this improved her cognitive functioning to about 80% of normal. On a subsequent visit I gave her a tiny sliver of a nitroglycerine tablet under her tongue. This totally relieved her fibromyalgia pain in about three minutes. I gave her several single dose samples to try at home on different days. Several agents did nothing for her. Then she called me to say that mestinon 30mg totally relieved her fatigue for about 8 hours. She is now taking nimodipine 60mg tid, mestinon 60mg tid ( the dose later had to be increased to maintain freedom from fatigue), and nitroglycerine, approximately 1/4 of a 0.3mg tablet sublingually as required. She has returned to work and has remained virtually symptom free on this regimen for almost two years.



I include the treatment protocol here for your consideration. Perhaps your own doctor would feel comfortable trying you on samples of some of them if he/she is not comfortable with all these potentially useful medications. (His most useful medications are: nimodipine, gabapentin, oxytocin, baclofen and I.V. lidocaine.)



For those of you who are interested in obtaining the full text of Dr.Goldsteins book, it has been published by The Haworth Medical Press and is available by calling 1-800-342-9678 .



I hope you find this information interesting. I wish you all a speedy recovery.

 

Sorry, graphics from Dr. Skerkey's review didn't make it in. Here is the orig. link:

http://www.ei-resource.org/articles...ry-by-dr-j-a-skerkey--betrayal-by-the-brain/

 

Hi Rockt

If you do a search on this site you'll find quite a bit of discussion on this. See for example:


http://forums.phoenixrising.me/showthread.php?5886-Nimodipine&highlight=nimodipine

Jenny

 

Thanks Jenny.

So, did you revisit this drug yourself? If so, has it helped. Also, do you know how Girlinthesnow is making out? I was going to PM her, but she doesn't have that function enabled.

My biggest problem, by far, is brain fog/cognitive difficulty. I can't watch tv, can only read brief newspaper and magazine articles, and driving and computer fatigue, (over-stimulate?), my brain rapidly. If I could improve on that, I'd have a bit of a life. I'm convinced that I don't have proper blood flow to my brain, so I'm eager to learn more about anything that might help in this regard.

 

Hi Rockt

No I haven't tried nimodipine again - been doing so many other things it would confuse things!

I do think it's worth trying - docs did tell me though that it's important to monitor blood pressure while on it.

Jenny

 

Thanks.

Yes, my BP, (and most of us, it seems), is generally pretty low. Dr. David Mason Brown, who is, I believe, the Scotish doctor who uses this drug to treat ME, advises starting slowly - 1/4-1/2 tablet every2-3 days - and work up, to avoid lowering BP.

 

KDM prescribed me some Nimotop, I started to take it again after reading this thread.

 

I like the sound of that book, and will be looking for it. As for the drug, I dunno. Mainly cos I think I take too many to begin with and adding another into the mix which has varying degress of efficacy is something I really don't want to do right now.

Thanks for the book synopsis and putting so much work into it.

 

Thanks Waverunner. Please let us know how it works for you. Wait, you've taken it before. How did it go before?

Have you heard how others have made out taking it?

 

Yeah, that's always a concern. I'm currently only taking clonazepam and I'm slowly tapering off. After the negative results of taking this particular benzo, I swore I'd never take another drug again. But... my brain symptoms are bad and are in fact the most debilating of this disease for me. If I can get back some brain function, I'll be able to live a little more, (well, that's an understatement - it would be HUGE!) Nomodopine seems pretty safe, too, though with pharaceuticals,you never know...

 

I am really sorry for your brain symptoms and the ensuing distress, I know that well. Hugs.

My reluctance comes from what I can only deem apathy - I'm tired of taking lotsa pills.

 

Hi Rockt,

currently I stopped taking it again because of headaches and lots of other stuff I take. I think it is very important that the rest of your body doesn't go through detox while you take nimotop. So the toxins etc. get transported away and not into the brain. I will take it again soon.

 

Thanks again Waverunner.

I'm very interested in the issue of toxins. I tested high for lead a few years ago and underwent several sessions of IV chelation, but many are saying that would not be adequate to eliminate all the lead, especially because of the lower permeability of the blood-brain barrier. Certainly didn't help with my symptoms.

The scotish doctor, (Dr. David Mason Brown), who advocated nimodopine suggested that the steady, gradual use of the drug will improve circulation to the brain and that will release toxins. Here's a link to Dr. Brown's info:

http://cfs-me.co.uk/

Are you thinking that one should undergo detox before using the nimodopine?

 

Well, I'm not sure. Nimodopine does not tighten the BBB to my knowledge so if you carry lots of toxins in your blood I don't know if it's wise to increase circulation to/in the brain. I guess it's better to detox first and then take nimodopine.

 

Unless, as Dr. Brown says, the increased circulation carries toxin out.

As always with this crazy condition, we don't know. I guess we just have to keep being human guinea pigs. Oh well, what have we got to lose?

 

Any recent feedback on nimodopine? Some how I am just coming across the information on it. I bought the ebook by Kristina Downing-Orr. I cant seemed to find anyone that has tried the whole protocol by Dr. Brown.

 

I have started using Nimodipine 3 weeks ago and I am currently on 1/4 tablet in the morning and 1/8 in the pm. I am following Dr Mason's protocol from the book : beating chronic fatigue, a complete step-by-step guide to recovery.

I seem to be having improvements but it is too early to be certain. Dr Mason says you will get worse before getting better, and it is the case for me. The drug is giving me side effects that are a replica of my symptoms. Today I was dizzy and nauseous for a good 3 hours. Weak in the legs and a bit of flushing in the face. I had to lie in bed, couldn't read or write because I was too dizzy. I felt bad in my when le body. According to the book, this is exactly what should be happening, so there is hope.

 

I just have to post a warning here. This is not a general criticism of Nimodipine or Dr. Goldstein.

We have a patient on this forum who has tested positive for antibodies to N-type calcium channels, but I have no idea if this is an isolated case. She had serious adverse responses to another calcium channel blocker, and now we know why. You don't want to "push through" symptoms which may involve heart function, as this does.

Dr. Mason may have a better way to tell what is going on, I simply don't know.

 

Thanks for the warning. Do you have a link to the thread about the antibodies ? I have been fine so far, except once where I was dizzy for a few hours. I thought today was the same, both episodes occurred 7 days after a dose increase.

But, as the symptoms are remaining as of now and I haven't taken my pm dose (half-life is about 8-10 hours), I am seriously considering I am crashing from my last gym training. I might have been over confident and pushed myself more than usual, to test how I would react. We'll see how long it takes me to return to my usual state. A crash from exercise usually lasts 4-5 days for me. If it is a crash, it's all my fault...

 

You may need to send a PM to the member. I send you the name.

If you are doing any kind of gym training you are a lot better off than others here. Better wait until your PEM (crash) runs out before you start anything new. One change at a time has been a good rule for me throughout this.