Nerve cells symptoms and conditions

I am re-posting this from June. I believe that we have many reasons to suspect that Singulair does indeed penetrate the blood brain barrier. I personally believe that under certain unusual conditions that Singulair can cause neurological damage. I tried before to put together a scenario of brain biochemistry that could explain how this can happen. Of course, I am just hypothesizing and all of my ideas will not prove to be totally correct. From the number of postings here regarding neurological symptoms, I believe that there is an answer out there somewhere. Why the FDA is not searching for this answer is a complete mystery to me.

I believe that it is possible that Singulair causes the same biochemical response in the brain that is cited in this study -- thus causing neurological damage.

"Thus, elevated NO production leading to mitochondrial dysfunction, glutamate release, and excitotoxicity may contribute to neuronal death in neurological diseases."

IS SINGULAIR CAUSING THE DEATH OF NERVE CELLS IN SOME PATIENTS? DOES THIS HAPPEN - ALTHOUGH INFREQUENTLY- BECAUSE OF GENETIC OR BIOCHEMICAL FACTORS OR BOTH?

June 12th
2008
2:56 AM
I have stated many times that I am not an expert. I just post what I find. This has been a mind boggling journey for me. This is way over my head but I struggle to read and understand. Finding answers to why children are suffering from neuro-psychiatric side effects is worth the effort.

I have made the following observations.

1. Some quinolines are known to be able to cross the blood brain barrier.
2. Molecules that ionize are known to be more likely to be able to cross cell membranes. So if montelukast ionizes as a result of change in blood pH to sufficient acid conditions, then it could be possible that it does in fact cross the blood brain barrier.
3. We know that there are cysLT1 receptors in the brain.
4. We know that researchers believe that montelukast may bind at the arginine of the cysLT1 receptor.
5. We know that arginine contains four nitrogens. And montelukast contains one.
6. We don't know what happens to those nitrogens. Are those nitrogens converted to nitric oxide?
7. We do know what macrophages create nitric oxide as I posted.
8. We do know that if something cause excessive nitric oxide to build in the brain that there would be damage to the neurons.

Some people may remember when I got stuck at the astrocytes, the cysLT1 receptors and glutamate. I keep looking for research reports that may shed more light on this.

Titre du document / Document title
Nitric oxide causes glutamate release from brain synaptosomes
Auteur(s) / Author(s)
MCNAUGHT K. S. P. (1) ; BROWN G. C. (1) ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
(1) Department of Biochemistry, University of Cambridge, Cambridge, ROYAUME-UNI
Résumé / Abstract
We determined the ability of pathological levels of nitric oxide (NO) to cause glutamate release from isolated rat brain nerve terminals using a fluorometric assay. It was found that NO (0.7 and 2 μM) produced (4 and 10 nmol/mg of synaptosomal protein) Ca2+-independent glutamate release from synaptosomes (after 1 min of exposure). Spermine/NO complex (spermine NONOate; a slow NO donor) and potassium cyanide (an inhibitor of cytochrome oxidase) also caused Ca2+-independent glutamate release. Preincubation of synaptosomes with 5 μM 1H- oxadiazole quinoxalin-1-one (an inhibitor of soluble guanylyl cyclase) had no effect on NO-induced Ca2+-independent glutamate release. Ca2+-independent glutamate release produced by NO was greater in a low-oxygen medium. NO, spermine NONOate, and potassium cyanide inhibited synaptosomal respiration with a similar order of potency with respect to their ability to cause glutamate release. Because NO has been shown previously to inhibit reversibly cytochrome oxidase in competition with oxygen, our findings in this study suggest that NO (and cyanide) causes glutamate release following inhibition of mitochondrial respiration at the level of cytochrome oxidase. Thus, elevated NO production leading to mitochondrial dysfunction, glutamate release, and excitotoxicty may contribute to neuronal death in neurological diseases.
Revue / Journal Title
Journal of neurochemistry ISSN 0022-3042 CODEN JONRA9
Source / Source
1998, vol. 70, no4, pp. 1541-1546 (29 ref.)

INIST-CNRS, Cote INIST : 4037, 35400007527188.0230

My 5 1/2 year old son began taking 4mg Singulair in the p.m. and an inhaler (asmanex) in the a.m. We were still having trouble controlling the asthma and his Sing dose was raised to 5mg. & within 1 week of the increase he began having terrible facial tics and aggravated behavior (defiant, poor listening, easily frustrated and angered) The tics were in the form of opening and closing his mouth, as if you were trying to clear your clogged ears after a plane flight. This caused him much pain in his jaws and facial muscles, so he would tic and then cry as he was in pain. This ramped up his anxiety and it made the ticking worse. He has been off of all asthma medication (cold turkey) for 5 full days. He has episodes where the tics happen for 10 min -1/2 hr, other times during the day it is one here and one there. He does not want to leave the house to do anything, even his favorite activities. Thank god I found this site (and others like it), as I got some answers and some hope. We went to see my cousin this week who is a neurologist and he never heard of the correlation of Singulair and neurologic side effects like these. He said that (hopefully) the medication side effects will cycle through and resolve the ticking and behavioral changes. If not we are probably looking at a Tic Disorder which is in the Tourettes Family.He put my son on a very low dose of Klonopin to mellow out his anxiety and help reduce the tics, but has only been on it for 1 1/2 days and it usually takes a wk or 2 for full absorption and results.I have since sent him and my pediatrician and allergist links to this site and others. I think that I see some improvement in my son, yesterday I thought he did better and my husband thought it was a worse day, I think we have totally lost our perspective and objectivity on this. If anyone out there has a time frame on when they saw significant recovery and positive changes I would love to hear from you. This is a total nightmare and if it is this drug, someone is going to pay. My prayers go out to all who are going thru this.

Many people have asked why I suggested that Omega-3 from fish oil MIGHT possibly help those retrying to recuperate from the adverse side effects of Singulair. It is my opinion, that it MIGHT help the body return to balance. And unless we OD on Omega-3 from dietary sources, (avoid tuna fish high in mercury), then it won't hurt.

Mechanisms and innovations

The science behind dietary omega-3 fatty acids
Marc E. Surette, PhD
Marc Surette is Professor and Canada Research Chair in Cellular Lipid Metabolism, Département de Chimie et Biochimie, Université de Moncton, Moncton, NB

Correspondence to: Dr. Marc Surette, Département

"When cells are activated by external stimuli, arachidonic acid is released from cell membranes and is transformed into powerful cellular mediators such as thromboxanes, prostaglandins and leukotrienes.10 These compounds possess a range of activities, including activation of leukocytes and platelets, regulation of gastric secretions, induction of bronchoconstriction and signaling of pain in nerve cells. The importance of these compounds in health and disease is evident by the range of pharmaceutical products that target their biosynthesis or action.11 Indeed, arachidonic acid metabolism is the target of nonsteroidal anti-inflammatory drugs (e.g., acetylsalicylic acid, ibuprofen), cyclooxygenase-2 (COX-2) inhibitors (e.g., rofecoxib, celecoxib12) and leukotriene antagonists (e.g., montelukast, zafirlukast).13 Dietary omega-3 fatty acids directly affect arachidonic acid metabolism because they displace arachidonic acid from membranes and compete with arachidonic acid for the enzymes that catalyze the biosynthesis of thromboxanes, prostaglandins and leukotrienes.8 Thus, the net effect of consuming foods enriched in omega-3 fatty acids is a diminished potential for cells like monocytes, neutrophils and eosinophils to synthesize these powerful arachidonic acid–derived mediators of inflammation and a diminished potential for platelets to produce the prothrombotic agent thromboxane A2." (Surette, 2008).

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My 17 year old daughter started Singulair last July for Asthma. She is brilliant and scored in the 99% on the ACT college entrance exam. She won 3 scholarships totaling over 60,000 and earned 27 college AP credits while still in high school, volunteering for the Red Cross, singing in choirs, and playing the lead in her high school musical and 3 plays. She was funny, sweet, and had many friends.
She left for college 3 weeks after starting the medication and saying she was breathing better. Her grades were terrible, even though I was able to check to see she went to class every session, as posted online. She became very depressed, withdrawn, staying in her dorm room. She was sleeping up to 20 hours straight without waking up. She didn't call her friends when she came home and only wanted to sleep. She was like a different person. She was so aggressive that she tried to run out in the middle of the night and attacked me when I tried to block her way, to the point I had to call the police. They diagnosed her with new onset major depression and ADD. They started her on Zoloft for 2 months and she got much worse and was removed from Zoloft as a result. She said she was too tired to stay awake even in class. We had a sleep study done for Narcolepsy and it was negative. Until reading these posts, I didn't connect the Singular. Everything I am reading is so familiar, it makes me feel ill. I can't believe I didn't know, I am a nurse. The guilt is horrible. I hope to get my daughter back, but she lost all her scholarships and only managed to pass 16 hours in one entire year of college. I can't afford to send her back without the money she lost. They even put her on a one time only probationary period to ever get Federal or State Financial aids and loans again. Singular had to be to blame. I am simply thankful my daughter is still here, she was very suicidal. My heart breaks for those of you that lost your children to the side effects of the drug. We have to get the word out by each filing a complaint to the FDA, and filling out adverse event forms.
Please don't let Merck get away with this. We need to act, even if your child was one of the lucky ones and is back to normal now.

Is there a potential explanation for the adverse psychiatric side effects of montelukast?

In my opinion, there are at least some very good clues based upon the work of the Chinese researchers.

A 2006 report indicated that they had localized (meaning found it was there) the CystLT1 receptor (same as the receptor that montelukast
Singulair blocks) in the neurons of the brain tissue of rats. In order to do that, they injected rat brain's with NMDA to cause a chemically induced state of excitotoxicity. Excitotoxicity is a common factor in Central Nervous System disease. They concluded that both 5-LOX and CystLT1 were upregulated by the excitotoxicity that they artificially created
with the NMDA. Therefore, there would be a potential link between neuron activity and CystLT1. Nerve cells are damaged by excitotoxicity. These researchers used NMDA to cause nerve damage which caused the CystLT1 to show up. NMDA was often used in human behavior studies to cause brain damage. They would then try to observe whether behavior was compromised to conclude what areas of the brain determined what behavioral response.

So I was thinking about the Chinese researchers as I was reading other posts. One post interested me particularly regarding the mother who described behavior that seemed like hypoglycemics when their snack doesn't arrive on time. So a light bulb went on. Glutamate, another excitotoxin, can build up in the brain to a level that is damaging if humans become excessively hypoglycemic. If glutamate concentration around the synaptic cleft reaches too high a level then neurons die. Clinically, it really does seem that many people experience things that sound like the effects of hypoglycemia. It could be only a coincidence. But then again, maybe not.

The Chinese researchers found the CystLT1 receptor in the rat brain neuron after brain damage. They found the CystLT1 receptor in the normal human brain in the microvascular endothelial cells and in neuron and glial-appearing cells in brain trauma or tumors.

What role does the CystLT1 play in brain function? If it exists in brain tissue, we can assume that it does have a function. If it plays a role in preventing or repairing neuron damage due to excitotoxins, then there would be a very direct link between Singulair and adverse psychiatric side effects.

http://www.chinaphar.com/1671-4083/27/1526.htm

The bottom line is that Merck owes people who take Singulair further research regarding it's effect on the brain.

I have read and heard, first hand, dozens of stories about Lipitor. It is clear why, too. When you cut off lipoproteins (commonly called "cholesterol"), you cut off the supply of essential fatty acids (EFAs) to the cell membranes of nerve cells, which use these EFAs for neurotransmission. Eventually the nerve cells degenerate and die, causing pain, stiffness, and loss of muscle control.

Typical: muscle pain, muscle weakness, swallowing problems, muscle cramps, numbness, spasms, muscle atrophy.

I'm aged 51 and have had high blood cholesterol for years, diagnosed in my mid thirties. Over the years I have tried changing diet but it didn't reduce tha bad cholesterol. Three years ago I decided maybe I better reduce the cholesterol as they say it clogs up you arteries etc. I went to the doctor and he put me on Lipitor and within a few months my levels were down to normal. I got joint pains in my hands, back, neck , legs and had sore heels after long walks. The doc then decided I'd go off the Lipitor to see if my levels stayed normal but they went back up. After a week the new pains had gone away. I came up with a plan to take 3 x 10mG a week rather than one each day and this worked with a lot less joint pain. The last test I had my levels are back up again so he put me back on 10mG a day and now three weeks later the pains have built back up and I don't like them. Desperate for a different solution I was listening to one of the Juice Plus promotions and something they said set me thinking. They said that having a high level of bad cholesterol doesn't always mean it will badly affect your arteries as it has to react with free radicals in your body to cause the damage. Their theory is that a diet rich in antioxidants will combat the free radicals and generally reduce the risk of disease which also includes any bad effects from high bad cholesterol. Now I'm wondering two things, how do I know if my high cholesterol is causing me any harm? is there a test I can get done to measure how it is or is not affecting me? Can anyone throw any more light on this?