Receptors symptoms and conditions

Hi. Im a nurse who was put in Topamax for mood stabilization in January of this year. Tapered up from 25 mg a night and now am on 200 mg a night. I have lost ZERO pounds although I have no appetite and cant stand the taste of a soda. I just wanted to share my nightmare. I have not had any tingling or numbness, which is a main side effect.

I do have a terrible metallic taste in my mouth and my mouth never feels clean. YUCK. Sodas flat. My personality is flat.. I am exhausted. My friends say the person they knew is gone, my appetite is gone.

My back hurts all the time like it's very tight in the kidney region....I cant spell, I cant remember yesterday, I sleep all the time when Im not working...I drop things, I don't remember what I was doing 10 minutes ago, I feel like I am on the outside of my body looking in.

My vision is blurred somewhat at times.

I work for a neuro-psychiatrist. I have decided to taper myself down. I don't think it has done anything but made me so flat I am not here anymore. Who wants that? Looking back, I was not in need of mood stabilization but a vacation.

The only thing it has helped me with is it has stopped the desire for Klonopin which is normal for Topamax. It works on the receptors in your brain that make you crave benzo's. I took my Klonopin as prescribed.

Im thinking I want my old self back. I miss laughter. :(

I am curious as to know if anyone else has experienced the same problems I seem to be experiencing now. I got my Mirena inserted Oct 28, 08 and bled heavily for 3 weeks. Since then I have had spotting every now and then but no period. I have cramps all the time and it feels sort of like being prego but I am not. I also have discharge all the time and it started after I got Mirena put in. I am trying to remain optimistic about this because I want it to work, will someone please give me some advice as to what I should do?
Thanks

How long does it take to be free of the side effects from taking Flomax? After being on 2 Flomax pills daily for over a year, I was still up 3x in the night. I stopped taking Flomax a month ago after reading here the side effects and realizing I suffered from many of them. Trouble sleeping, sinus headaches, almost zero libido etc. Question...when will the libido return?
R. (Ontario)

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

Since HTML is not allowed...need you to find the links to the following:

"whether an oral contraceptive (OC) containing drospirenone (DRSP) (3 mg) + ethinyl estradiol (EE) (30 μg) (DRSP + EE) could modify psychological symptoms and whether it could modify steroids interfering with the γ-aminobutyric acid (GABA)-A receptors.

Conclusion(s): The results suggest beneficial effects of DRSP + EE on psychological symptoms by

decreasing DHEAS."

Beneficial to lower the levels of DHEAS?!

"Women With Higher Levels Of DHEAS Have Better Cognitive Function"

"dehydroepiandrosterone sulfate (DHEAS), inhibit the production of TNF in vitro and in vivo."

Who is at greater risk?

Those who have the HLA-DR gene type and already have allergies/asthma.

Adrenergically blockaded conditions = AdBCs include the following: respiratory allergies, skin allergies, and asthma.

IgE will go thru the roof. Allergic reaction. Th2 pathway.

""It has also been shown that young women exposed to intensive stress situations,

with low plasma of dehydroepiandrosterone
sulfate (DHEA-S),

and a recent use of contraceptive pills are most at risk for

onset of autoimmune disease."

Below is the latest ADR report on Singulair from the United Kingdom. I deleted side effects reports by very small numbers of patients in order to keep the post briefer. This shows the total number of reports since Singulair was approved in the UK.

I don't know the total number of prescriptions for Singulair in the UK. It is considered expensive.

Drug Analysis Print
Drug name: MONTELUKAST
Drug name: MONTELUKAST Report type: Spontaneous
Report run date: 13-May-2008 Report origin: UNITED KINGDOM
Data lock date: 09-May-2008 08:00:02 PM Route of admin: ALL
Period covered: 01-Jul-1963 to 09-May-2008 Reporter type: ALL
Earliest reaction date: 01-Jan-1997 Reaction: ALL

Cardiac disorders-TOTAL 64
Palpitations 29
Myocardial infarction 6
Tachycardia 6
Diarrhoea 84
Dyspepsia 24
Abdominal pain 98
Abdominal pain upper 22
Nausea 84
Vomiting 52
Dry mouth 15
Asthenia 13
Fatigue 45
Malaise 32
Sudden death 1
Pyrexia 10
Chest discomfort 12
Feeling abnormal 16
Influenza like illness 17
Irritability 18
Drug interaction 13
Chest pain 13
Arthralgia 59
Myalgia 38
Muscle spasms 24
Pain in extremity 14
Balance disorder 10
Lethargy 16
Somnolence 23
Psychomotor hyperactivity 25
Headache 221
Dizziness 68
Neuropathy peripheral 7
Convulsion 6
Epilepsy 7
Dysgeusia 7
Hypoaesthesia 6
Tremor 18
Nervous system disorders TOTAL 526
Abnormal behaviour 13
Agitation 12
Anxiety 18
Aggression 30
Depression 23
Insomnia 58
Abnormal dreams 12
Nightmare 49
Hallucination 21
Sleep disorder 15
Psychiatric disorders TOTAL 364
Asthma 36
Allergic granulomatous angiitis 43
Angioedema 12
Swelling face 12
Erythema 13
Pruritus 32
Rash pruritic 17
Rash 55
Urticaria 33

TOTAL NUMBER OF REACTIONS 2841
TOTAL NUMBER OF FATAL ADR REPORTS* 19
TOTAL NUMBER OF ADR REPORTS* 1489

How does montelukast affect laminin beta2? I don't know but this came up when I cross referenced N106A.

Synthesis of tenascin and laminin beta2 chain in human bronchial epithelial cells is enhanced by cysteinyl leukotrienes via CysLT1 receptor

Cysteinyl leukotrienes (CysLTs) are key mediators of asthma, but their role in the genesis of airway remodeling is insufficiently understood. Recent evidence suggests that increased expression of tenascin (Tn) and laminin (Ln) beta2 chain is indicative of the remodeling activity in asthma, but represents also an example of deposition of extracellular matrix, which affects the airway wall compliance.

We tested the hypothesis that CysLTs affect production of Tn and Ln beta2 chain by human bronchial epithelial cells and elucidated, which of the CysLT receptors, CysLT1 or CysLT2, mediate this effect.

Methods: Cultured BEAS-2B human bronchial epithelial cells were stimulated with leukotriene D4 (LTD4) and E4 (LTE4) and evaluated by immunocytochemistry, Western blotting, flow cytometry, and RT-PCR.

CysLT receptors were differentially blocked with use of montelukast or BAY u9773.

Results: LTD4 and LTE4 significantly augmented the expression of Tn, whereas LTD4, distinctly from LTE4, was able to increase also the Ln beta2 chain.

Although the expression of CysLT2 prevailed over that of CysLT1, the up-regulation of Tn and Ln beta2 chain by CysLTs was completely blocked by the CysLT1-selective antagonist montelukast with no difference between montelukast and the dual antagonist BAY u9773 for the inhibitory capacity.

Conclusion: These findings suggest that the CysLT-induced up-regulation of Tn and Ln beta2 chain, an important epithelium-linked aspect of airway remodeling, is mediated predominantly by the CysLT1 receptor.

The results provide a novel aspect to support the use of CysLT1 receptor antagonists in the anti-remodeling treatment of asthma.

Author: Siiri Altraja, Martin Kadai, Erki Rekker and Alan Altraja
Credits/Source: Respiratory Research 2008, 9:44

Published on: 2008-05-26

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 quinoline 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 that it ionizes, then it could be possible or maybe like 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.
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

Montelukast - quinoline cysLT1 receptor antagonist

In some cases the introduction of a 7-chlorine atom to the quinoline ring proved beneficial. Correlation of the pKa values of the quinoline nitrogenwith the CysLT1 receptors affinities was reported indicating a possible hydrogen bond interaction between the quinoine nitrogen and the receptor.
The quinoline moiety or its equivalents is suggested to mimic the lipophilic region of the CysLT and the acidic groups mimick either the peptide or the eiocosanoid tail of CysLT.

The resulting model figure 12 suggests multiple intereactions between the antagonists and the arginine residue. Besides the hydrogen bonds between the acidic residues and the guanidine moiety of arginine, quinoline containing CysLT1 antagonists are shown toe form an additional
hydrogen bond beetween the quinoline nitrogen and a guanidine hydrogen atom. This interaction may be an explanation for the importance of the presence and position of a nitrogen atom, as observed for most CysLT1 antagonists of the quinoline class. In addition the antagonists were found to wrap around the arginine and thus "short molecules such as WY48252 are easily fitted in the model. i.e. the variable spacers between the lipophilic and the acidic groups do not post major restrictions to the receptor affinity as long as they are flexible enough to allow
the acidic groups to bend back for interaction with the arginine. The incorporation of Montelukast in the model suggests the presence of an additional binding pocket....Since the affinity of LTD4 itself was little affected, arginine residues were suggested to be important for the binding of antagonists but not for LTD4. These results sustained our relucrtance to derive an antagonist model based on structural similarity
between the agonists and antagonists.

Ming-Qiang Zhang and Mariel Zwaagstra

Current Medicinal Chemistry, 1997, Vol. 4, Nov. 4.

Sorry, I can't just walk away.

When you find patents or patent applications for certain purposes, then you know that your ideas are well founded. There are several patents for using an anti-malaria drug for asthma. I would bet that somebody had that idea all the way back to the 1960's. So it is very possibly no coincidence at all that a chloroquinoline or other quinoline ring would be part of montelukast's chemical structure.

Here is one of the patents.

******

It is well known that quinoline rings can be toxic to some people even very rapidly. As in this very extreme example.
--------------------------------------------------------------------------

PEDIATRICS Vol. 27 No. 1 January 1961, pp. 95-102 This Article

FATAL ACUTE CHLOROQUINE POISONING IN CHILDREN
Howard M. Cann M.D.1 and Henry L. Verhulst M.S.1

1 National Clearinghouse for Poison Control Centers, Accident Prevention Program, Public Health Service, U. S. Department of Health, Education, and Welfare
Four cases of acute chloroquine poisoning in children are presented. In three instances death occurred within 2 hours of ingestion of larger than therapeutic amounts of the drug. The rapid occurrence of death in acute chloroquine poisoning is probably explained by complete and rapid absorption of the drug from the gastrointestinal tract resulting in high blood concentrations which depress vasomotor function and respiration. Cardiac arrest follows and may be caused by the direct myocardial action of chloroquine, to anoxia, or to both. The similarity of the manifestations of acute chloroquine poisoning and those of acute quinine and quinidine poisoning suggests that acute toxicity may be attributed to the quinoline ring portion of these drugs.

----------------------------------------------------------------------------------

I don't think that we are seeing extreme examples. But we may be seeing less extreme immediate reactions or reactions where the toxicity builds up over time.

Quinoline rings are know to cause neurotoxicity. There are theories about how that happens. One of the theories is about blocking connexins which are gap junction proteins in the brains.

I don't know how montelukast could be breaking up so that it causes toxicity. Or if the problem is the how rapidly the liver enzymes can metabolize it. But there is plenty, plenty, plenty of clinical evidence that there is a quinoline ring culprit somewhere in the picture. Or some by-product of that causing problems.

Somehow it was decided that montelukast did not have the safety issues that the other drugs in the same category have. See this.

"The starting point in the development of montelukast appears to be a quinoline-containing structure, likely identified as a weak random screening lead (Figure 3). The Merck group hypothesized that this molecule was mimicking the olefin backbone of cysLTs, and that the addition of mimics for the acid and peptide regions of LTD4, might improve its potency. As a first step, the dithioacetal linkage first seen in some SmithKline compounds was incorporated; this led to a compound with greatly increased in vitro potency but poor oral bioavailability. When one of the carboxylic acids was replaced by an amide, forming MK-571, the new antagonist had even greater potency and good efficacy following oral administration. The enantiomers were resolved to yield MK-679 (verlukast), a compound with better clinical effects than MK-571, but whose clinical development was stopped for safety reasons. Further structure-activity relationship studies led to the development of montelukast (16), an antagonist that appears free of the safety concerns plaguing earlier members of this series."

If we can find out why the earlier versions were not safe and how they thought fixed it, then maybe we can find out what is going on with the quinoline ring in some people.

I would be very surprised if the FDA will address our concerns. Why does it always seem like they wait for enough people to die like in Vioxx? Wasn't Vioxx responsible for thousands of deaths?

OH and to those of you have taken the time to read these posts and have posted your own accounts and have not been offensive. Thank you! I appreciate you increasing awareness. Concerned citizen I am very thankful that you have done so much research. It has been very useful to me!

I spent the weekend reading about the development of Singulair. The early studies recognized that the first phase of the acute asthma response bronco-constriction was probably not caused by leukotrienes. They identified histamines and prostaglandins as the probable sources. I don't think that changed because the Singulair literature states that it should not be considered as a treatment for that. Leukotrienes were a source of inflammation caused by eosinophils and mast cells present in greater numbers (than normal) in airway tissue. So, it was beneficial to find a way to decrease that.

The cysLT1 receptor was identified as source of the signals that tell the cells to produce leukotriene. The receptor, a gene, consist of 337 (they think) amino acids. They modified a compound that would bind to that receptor thus blocking the cells ability to produce leukotrienes. This compound is very specific. It was formulated to bind to the "model" receptor. This compound will not even bind to cysLT receptor sub-types. (That is the good thing.) There is an enormous amount of research that discusses the genetic variability of the chemical reactions that occur in the leukotriene (calling it this for simplicity) pathway. We are also seeing that a number of researchers would like to use gene profiles to predict whether patients will respond favorably to different asthma/allergy drugs. ALL PATIENTS HAVE A RIGHT TO KNOW IF IT IS INHERENT THAT SOME PEOPLE WILL NOT RESPOND TO SINGULAIR OR RESPOND ADVERSELY.

There are many studies from the 1998 era that conclude that montelukast is not effective for everyone. Those researchers stated that it can be predicted that those people who are going to respond favorably will do that within the first 14 days or so. That conclusion would be consistent with a genetic component for efficacy and safety of Singulair. Those doctors concluded that those who did not respond within that time frame should not take Singulair for fear of harming them. That makes good sense.

The Italian researchers wanted to know if there was more going on than blocking leukotrienes in the action of montelukast. They set up a "test tube" study regarding montelukast, the cysLT1 receptor, and some t-cells that they selected. Why? Researchers always have something on their minds. They observed the death of these particular t-cells.

Montelukast is a quinoline. We basically know of quinilines and quinolones as compounds that were invented as broad spectrum antibiotics. They work because they interference with bacterial DNA so they cannot replicate themselves. Montelukast is a quinoline modified to bind with the cysLT1 receptor (a gene) and prevent that gene from activating. That's consistent with what a quinoline/quinolone does.

So what does montelukast do in blood plasma if it does not bind to the receptor because of genetic mis-match? (If montelukast does bind, then a chemical reaction has occurred and the liver will break down the by-products. Montelukast metabolized in 10-12 hours.) What happens if it doesn't bind? How long before it breaks down? Does it produce toxic by-products?

I want to know what happens to lymphocytes such as t-cells just because montelukast is a quinoline. Maybe nothing but what's up with the Italians researchers? I want to know if montelukast has the capability to interfere with lymphocytes who can clone themselves. That could be a good thing under circumstances when these lymphocytes are causing inflammation. But it could be a bad thing in the case of normal individuals with no problems.

I want to know if the bad side effects are due to the fact that the body has to break down and metabolize a quinoline that did not bind to the receptor for which it was created. The side effects of Singulair are strangely similar to what is observed in the quinolones such as levaquin. I have not as yet been able to compare montelukast as a quinoline to levaquin as a quinolone. I am hoping to find something on these categories. There may be no reason to worry that they cause similar damage. But frankly, I think that there is. There is some terrible chit happening to some people. The scariest is the neurological damage.

All of these questions would be in the everybody pharma knows to ask category. I don't know where the answers are. I haven't found them as of yet. Maybe there are no answers. We have to remember that Singulair and Vioxx were released in the same year. They have continued to be drugs under the current executive management of Merck. If the Vioxx marketing promoters had their ghost writers, why not the Singulair marketing promoters. The genetic component appears to be widely accepted but we haven't heard one thing about even that.

I think that it is sad that maybe the marketing of Singulair as one stop shopping for asthma/allergies may have destroyed the original concept. I really think from reading the original work that they knew that they couldn't engineer a drug for one size fits all. Everybody gets harmed when information is withheld.

Shame on the allergist who yelled at the mother who wanted to discuss issues. Does he know exactly who is allergic to Singulair and who isn't? Get him a dunce hat. Just because Singulair is marketed for allergies does not mean that you cannot be allergic to it. See the power of Madison Avenue? The ad agencies focus group these drugs to death. The ad agencies cleverly craft the product information. A good piece of legislation would be to prohibit consumer drugs ads.

Neurological problems and the effects of Singulair should be investigated. The Chinese researchers demonstrated that the CysLT1 receptor (singulair inhibits this receptor) does exist in the human brain. In the rat brain, they demonstrated that there is a link between this receptor and the astrocyte.

There are many researchers/doctors interested in excitotoxicity and damage to neurons.

http://www.jpands.org/vol9no2/blaylock.pdf

I would like to know how Singulair affects the astrocyte numbers and function. I would also like to know if there is a link between metabolism and the cysLT1 receptors in gastro-intestinal mucosa. Does Singulair affect the metabolic process?

So many parents are complaining of ADD/ADHD symptoms? The paper that I gave you the link correlates the immune response and excitotoxicity. That is very interesting. How many asthma and allergy patients also suffer from potential excitotoxicity? Does Singulair cause it in some patients or just make it worse in some patients? None the less--there is a possible link.

Why the brain function is impaired due to Singulair????? Maybe.

Here is the last chapter in a theoretical reason why Singulair affects brain function thus causing anxiety, depression, agitation, aggression, ADD/ADHD, and in extreme situations maybe seizures. I presented the study of the Chinese researchers that show a direct link between the cysLT1 receptor and the astrocyte in the brain. We don't really know how the cysLT1 receptor interacts with receptors that control astrocytes under all circumstances. We just know that there is an important link.

So last night, I had a dream about astrocytes. I don't really have anything to do but sit on an island, look at the Caribbean and fish so mental stimulation is actually welcome.

The last part of the "chain reaction" is probably the astrocytes role in glyconeogenesis. In other words, when the brain does not get proper nutrition, it sends signals to the liver to do something about the problem. The liver in turn releases glycogen which is turned into glucose to be released into the blood stream. A very unhappy brain becomes a very relieved brain. Obviously, we can't be eating all day long to keep our blood sugar up so the liver has to store energy and release it at the correct time.

Here is a diagram of that. Astrocytes are the only cell that produce the proper chemicals for this process to happen.

http://www.nature.com/jcbfm/journal/v27/n2/fig_tab/9600343f5.html
FIGURE
Quote: All credit to the authors, of course.

Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis
Leif Hertz, Liang Peng and Gerald A Dienel

BACK TO ARTICLEFigure 5.
Next figure | Previous figure | Figure and tables index

Glucose utilization pathways that provide or consume ATP. (A) Schematic of key aspects of the glycolytic pathway of glucose utilization for energy metabolism and major branch points that can divert carbon for other uses, including NADPH generation, storage of glucosyl units in glycogen, neuromodulator, and amino acid and nucleotide biosynthesis. The most important reactions for generation of energy are glycolysis (pyruvate/lactate formation from glucose), shown in light brown and occurring in all cell types, and glycogenolysis (pyruvate/lactate formation from glycogen), shown in light green, which occurs only in astrocytes, due to the astrocyte-specific expression of the enzyme glycogen phosphorylase, which releases a glucosyl unit from glycogen as G1P. The energetically most important biosynthetic reactions are synthesis of glycogen from glucose (glycogenesis) shown in brown and green and from pyruvate/lactate (gluconeogenesis) shown in pink, brown, and green. Gluconeogenesis is also astrocyte-specific, because only astrocytes express fructose-1, 6-bisphosphatase, which generates F6P from fructose-1, 6-bisphosphate (F1, 6P) and PC, which generates oxaloacetate (OAA) from pyruvate. The latter reaction is followed by formation of phosphoenolpyruvate (PEP) by decarboxylation of OAA; this sequence is necessary to form PEP from pyruvate, an energetically unfavorable reaction. Biosynthesis of serine/glycine (shown in olive) is also an astrocyte-specific process due to preferential expression of 3-phosphoglycerate dehydrogenase (Yamasaki et al., 2001). Both neurons and astrocytes form alanine and ribose-5-phosphate (R5P), the latter in the pentose shunt pathway (upper left corner), linked to NADPH production needed for operation of glutathione peroxidase and oxidation of monoamine transmitters. The MAS, indicated by red, transfers malate formed in the cytosol from oxaloacetate during conversion of NADH to NAD+ into mitochondria. PDH-mediated formation of acetyl CoA, which is also shown in red, initiates oxidative degradation of pyruvate in the mitochondria. Red and blue text for ATP indicates energy production and utilization, respectively. (B) Major reactions and net ATP yields or net ATP consumption of major pathways derived from the glycolytic pathway are indicated in color-coded boxes that correspond to the color-coded pathways in panel A. For simplicity, the scheme indicates the energy yields (ATP) and NAD(P)H production or utilization based on metabolism of 1 glucose to form one ribulose-5-P, two lactate/pyruvate, or 2 serine; a similar representation illustrates the energy and cofactors required for gluconeogenic conversion of two moles of lactate into one free (G6P) or glycogen-bound glucosyl unit. Glc, glucose; P, phosphate; G6P, glucose-6-P; 6PG, 6-P-gluconate; R5P, ribulose-5-P; GSH, reduced form of glutathione; GSSG, oxidized form of glutathione; F6P, fructose-6-P; F1, 6-P, fructose-1, 6-bisphosphate; GAP, glyceraldehyde-3-P; DHAP, dihydroxyacetone-P; 3PG, 3-P-glycerate; 2PG, 2-P-glycerate; PEP, phosphoenolpyruvate; Pyr, pyruvate; Lac, lactate; Ala, alanine; OAA, oxaloacetate; 3P-HyPyr, 3-P-hydoxypyruvate; Glu, glutamate; KG, -ketoglutarate; 3P-L-Ser, 3P-L-serine; L-ser, L-serine; D-ser, D-serine; Gly, glycine; C1, one carbon fragment used for methyl donor reactions.

This is quite interesting because should the connection between the cysLT1 receptor and astrocyte be established and explained, it shows that there is a very direct link between the immune system and metabolism. That should be intuitive because when we get seriously sick, then we are laying in bed and the body should try to conserve energy so that we don't just waste away.

So what happens if we cause changes in the cysLT1 receptor to cause the astrocytes to believe that we are sick, the normal connection between the brain and glyconeogenesis then doesn't exist. We would have to be causing some kind of periods of extreme stress on the brain because we are out moving around and doing not home sick in bed.

Maybe we should award the Chinese researchers the nobel prize? Maybe they established the connection between the immune system and metabolism? Is there also a link between the immune system of some individuals and depression? Some how, this makes perfect sense. So we have to find out and help as many people as we can.

I think that it is time to call the lawyer-biochemists to find out if this can be proven to be true and if Merck knew or not.

Singulair does interact with the astrocyte in the brain.

The role of the cysLT1 receptor (Singulair blocks this receptor) and the astrocyte in the brain has been studied. For anyone from Merck to say that there are no mechanisms by which Singulair can affect the
brain is ludicrous. If the Chinese researchers are correct, then Singulair very clearly affects the brain. Certainly, we don't know exactly how or when the effect would be good or bad. Under what circumstances would it be beneficial and under what circumstances would it be harmful.

For quite a while, researchers have been hypothesizing about the role of the astrocyte in brain function. If we go to look for theories, we will find them. Here is the theory of Dr. Dale Antanitus. I am no here to promote anyone's theory in particular but just to point out that they exist.

http://www.antanitus.com/hypothesis

We can see that the Chinese researchers have gone forward to look at potential links between the cysLT1 receptor (Singulair receptor) and inflammatory response in the brain. The 2008 study showed a link between the astrocyte and the cysLT1 receptor (Singulair receptor)

1: Glia. 2008 Jan 1;56(1):27-37. Links
Activation of CysLT receptors induces astrocyte proliferation and death after oxygen-glucose deprivation.

Huang XJ, Zhang WP, Li CT, Shi WZ, Fang SH, Lu YB, Chen Z, Wei EQ.
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, People's Republic of China.

We recently found that 5-lipoxygenase (5-LOX) is activated to produce cysteinyl leukotrienes (CysLTs), and CysLTs may cause neuronal injury and astrocytosis through activation of CysLT(1) and CysLT(2) receptors in the brain after focal cerebral ischemia. However, the property of astrocyte responses to in vitro ischemic injury is not clear; whether 5-LOX, CysLTs, and their receptors are also involved in the responses of ischemic astrocytes remains unknown. In the present study, we performed oxygen-glucose deprivation (OGD) followed by recovery to induce ischemic-like injury in the cultured rat astrocytes. We found that 1-h OGD did not injure astrocytes (sub-lethal OGD) but induced astrocyte proliferation 48 and 72 h after recovery; whereas 4-h OGD moderately injured the cells (moderate OGD) and led to death 24-72 h after recovery. Inhibition of phospholipase A(2) and 5-LOX attenuated both the proliferation and death. Sub-lethal and moderate OGD enhanced the production of CysLTs that was inhibited by 5-LOX inhibitors. Sub-lethal OGD increased the expressions of CysLT(1) receptor mRNA and protein, while moderate OGD induced the expression of CysLT(2) receptor mRNA. Exogenously applied leukotriene D(4) (LTD(4)) induced astrocyte proliferation at 1-10 nM and astrocyte death at 100-1,000 nM. The CysLT(1) receptor antagonist montelukast attenuated astrocyte proliferation, the CysLT(2) receptor antagonist BAY cysLT2 reversed astrocyte death, and the dual CysLT receptor antagonist BAY u9773 exhibited both effects. In addition, LTD(4) (100 nM) increased the expression of CysLT(2) receptor mRNA. Thus, in vitro ischemia activates astrocyte 5-LOX to produce CysLTs, and CysLTs result in CysLT(1) receptor-mediated proliferation and CysLT(2) receptor-mediated death. (c) 2007 Wiley-Liss, Inc.

PMID: 17910051

The astrocyte has been studied to see how it functions in the brain. The astrocyte:

1. may perform a role in the physical structuring of the brain
2. may perform a role in providing neurons with nutrients
3. may perform a minor role in the maintenance of the blood brain barrier
4. may perform a role in neurotransmitters
5. may perform a role in the regulation of ion concentration in the extracellular spaces
6. may perform a role in neuronal regulation of blood flood
7. may perform a role in the protection and repair of neurons

TO LIE TO PEOPLE REGARDING THEIR HEALTH IS CRIMINAL AND SHOULD BE PROSECUTED. PEOPLE OUT THERE ARE GETTING SICKER IF THEY ARE EXPERIENCING SIDE EFFECTS BECAUSE MERCK IS LYING. SOME PEOPLE MAY NOT EXPERIENCE SIDE EFFECTS BUT WHY NOT TELL THE TRUTH AND SAY THAT THERE COULD BE SOME PEOPLE WHO HAVE PSYCHIATRIC SIDE EFFECTS BECAUSE THERE IS A PATHWAY FOR THAT TO HAPPEN.

One of the most important questions we should be asking as parents is:

How does Singulair - a leukotriene receptor antagonist (blocks the receptors) affect the normal function of the mast cell?

The mast cell is the FRONT LINE DEFENSE against invading micro-organisms. When Singulair was invented, there was limited knowledge regarding the mechanisms by which the mast cell performed it's function. In my opinion, the focus was very narrow - those interested zeroed in on how the leukotriene receptor performed a role in the cause of asthma attacks and how ashma attacks could be prevented. Well, that's good preventing asthma attacks. But what happens to the mast cell if that receptor is blocked on a long term basis. I am not suggesting that blocking the receptor is bad but what if the long term effect is different than what we are are lead to believe-which is this is a safe medication with no known long term effects. What if the leukotriene receptor was just blocked short term a week or two to allow the body to clean up the mess from the last attack?

I seriously question what is going on with all of these infections. Are they related to crippling the mast cell? Parents should be allowed to question. If Merck doesn't want to answer questions regarding what happens to the mast cell (including are the numbers of mast cell decreased on Singulair), then something really BIG is missing. If by any chance (unknown at the moment) that the mast cell is significantly changed and therapy by montelukast is proper on a short but not long term basis, so freakin' what if Singulair is not a huge money maker any more.

Parents deserve every answer possible when decisions regarding their child's growth and development is on the line. I hope that we get some answers.

Of course, what was there in 2002 were new questions-not necessarily answers about the mast cell. Did anybody apply this to Singulair studies?
May 2002

From Journal of Clinical Investigation

Pattern recognition receptors on mast cells
The Toll-like receptors (TLRs) fit the definition of pattern-recognition molecules, which were originally postulated to allow the innate immune system to detect the 'molecular signatures' of various infectious agents. Although the innate immune system has no memory, it shows a degree of specificity, in part because the various TLRs recognize different sets of pathogen-associated molecules. Dermal mast cells are usually associated, not with the innate immune system, but with atopic dermatitis, but Supajatura et al. have found that these cells also express TLRs. They report here that TLR4, which binds the gram-negative product lipopolysaccharide (LPS), and TLR2, which binds peptidoglycan (PGN) from gram-positive organisms like Staphylococcus aureus, induce distinct mast cell responses. Staphylococcus is known to exacerbate allergic dermatitis, but it has generally been thought to act by inducing antibacterial IgE's, which trigger mast cell degranulation by stimulating the IgE receptor. Interestingly, the authors show that the interaction between PGN and TLR2 can provoke mast cell degranulation directly, sidestepping the need for IgE receptor engagement.

I am repeating one of my post regarding the Swedish study of the side effects of Singulair. When I read that parents have complained to their doctors about side effects and been dismissed, and told to continue the medication, I truly questions whether these doctors are giving their patients the right to INFORMED CONSENT.

I have been told by doctors before something like this "That is my professional opinion - I stand by it ." And I have said right back-- I understand that is your opinion. But if you don't have the time to tell me what I need to know then I am not giving you my informed consent. I get an entirely different attitude after that point. Because, that is how doctors get sued. Parents/patients didn't understand.

1. Have parents been told the complete reasons why it would be absolutely necessary, just necessary, or desirable to take Singulair and why?
2. Have parents been told what the alternative treatments are and the possible side effects of those treatments?
3. Have parents been given an option of another treatment when they complaint about the side effects of Singulair?
4. Do parents know that headache is a side effect that occurs in 18% of patients? These headache have indicated some serious events in European hospital reports. They are not just sinus headaches.
5. Do parents know that Singulair can cause serious events that require hospitalization as referenced in European hospital reports? These reports have described the event and provided laboratory test results that prove that Singulair was the cause.
6. Singulair in NOT an anti-histamine. Can your doctor fully explain to you how Singulair interacts with the receptors on the mast cell (cell part of the immune system)? Can your doctor fully explain how the mast cell will be changed by this? The mast cell has a number of receptors that interact with each other to tell the mast cell how to function normally; when it's time to die; when it's time to be replaced; and when to tell the bone marrow to send a replacement mast cell. Singular CHANGES the immune system---- good or bad???

So here is the report from Sweden to take to your doctors. Would your doctor give consent for his/her children after reading this? Maybe he/she would BUT at the very least that doctor would be looking for side effects that could mean trouble.

------------------------------------------------------------------------------

Update: I have spent hours searching scientific data bases for articles on Singulair. So far this is the most direct reference to adverse drug reactions and Singular.

For anyone who wanted to print the article from the Swedish researchers that stated that their study suggested that montelukast (singulair) should be investigated for adverse psychiatric drug reactions, I was able to find a link with open access to the public. So far, this is the only article that I have found. I am still searching through databases. This link should work if you cut and past. I am sure that all doctors would appreciate the opportunity to read it for themselves to see what they think.

PRINT REPORT.

http://www.biomedcentral.com/1472-6904/8/1

Individual case safety reports in children in commonly used drug groups – signal detection Gertrud Brunlöf , Carina Tukukino and Susanna M Wallerstedt Department of Clinical Pharmacology and Regional Pharmacovigilance Centre, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden author email corresponding author email BMC Clinical Pharmacology 2008, 8:1doi:10.1186/1472-6904-8-1 Conclusion In conclusion, the present study indicates that ADRs are reported for commonly used drugs in children. The number of ICSRs varies in different groups of drugs. A possible signal for montelukast and psychiatric adverse drug reactions was found, which should be further explored.

Please don't forget to PRINT the Tables which open on a separate page. Table 2 lists the specific side effects that they found which include anxiety, aggression, night mares, pain, and several others.

about 1 hour ago on Apr 13, 2008 by artie81, #7148
You are a retired what? Did you ever hear of the blood brain barrier? I know receptors exist in all cells. You obviuosly are not a physician.

Artie, what does retired have to do with blood brain barrier?

Who out there in the pharmaceutical industry would speak if they thought that his/her life would be the same as Jeffrey Wigand? Probably only people retired.

Merck's own website states that Singulair is not an anti-histamine. I cannot imagine any General Practitioner receiving a clear picture of how Singulair actually works from this site. Nor, are they being presented with the truth about the side effects. The whole site is a bunch of marketing FLUFF that never gets to the point. At the very least, the GP's should be on the rampage with us for being deceived.

I plan to rant about this later. What a dumbed-down presentation (Merck's site)? What an insult?

http://www.singulair.com/montelukast_sodium/singulair/hcp/allergies/efficacy/index.jsp

I just got a very condescending private message from a doctor on this site who said that while my articles from Europe are very helpful that I don't know what I am talking about and that I could mislead the public. Then I see how many parents and patients got a condescending attitude from their own doctors.

Well the public has been mislead but it is not my fault. I don't see any experts in this field stepping up to the plate to acknowledge that these side effects exist, have been reported by authorities in other countries, and that these experts are interested in learning why they are happening. This is an extremely widely prescribed medication that involves the lives of millions.

Merck's research director was quoted as saying that they know of no mechanisms by which these side effects could be related to psychiatric adverse drug reactions. That was a flat out LIE. So what if I quoted you a research article from China that was very complicated and yes, could possibly be misinterpreted by somebody? I just needed to give you an example. The only expert so far that had the guts to give you a truthful statement was Dr. J. Douglas Bremner. Thankfully, he corrected a misunderstanding about saying that it was "unclear."

I hope that we will all hang in there and something will be said by somebody, anybody on this site that will make the FDA listen and investigate Singulair (montelukast) all the way back to the very original studies done in test tubes not on people. And, then take a new look at it from the standpoint of what we now know about human genetics. I guess I will keep repeating myself about one size does not fit all.

I would also PRAY that all clinical studies on Singulair (montelukast) would be suspended until the FDA decides why these side effects occur. And that they would issue a statement to doctors to make conservative decisions regarding treatment with Singulair until the results of the investigation have been reported.

I hope that nobody thinks that I am trying to mislead anyone. The answers are either unknown or being hidden by Merck. How would I know the answers? I don't work for Merck. How many other people are out there trying to translate articles in foreign languages to see what's going on? American doctors are calling Merck and being assured that there is nothing to these claims.

I wonder how many experts there are that just don't want to be another Jeffrey Wigand or don't know what is wrong?

I know that I am ranting but somebody should do it.

I don't think I will find much more to research. If you have allergies or asthma, the immune system has become hyper sensitive. But, we cannot allow medications to suppress our immune system in general for the sake of controlling certain symptoms that we are having. Everything in the immune system has a purpose. So good sense would tell us to use as little intervention as possible to keep the entire system running. How to do that is very individual.

If you have a hyper allergic children, read about the immune system first so that you can ask your doctor the questions that you need to ask. Try going to a site that is written for the public.

http://www.howstuffworks.com/immune-system.htm

If your doctor cannot explain how a medication works and only knows that it's FDA approved for asthma or allergies, then on to the next. Any doctor should be able to explain if one part of the immune system is suppressed what happens to the other parts. If you ask the question, what happens to the nasal passages if the receptors are suppressed and the neutrophils don't know that there is an infection? Will my child be more inclined to get sinus and upper respiratory infections? That is just one example.

I am disheartened but not surprised that so many doctors are dismissing these reports of symptoms that patients have had after taking Singulair. The only reports that I have found to share with you are from Europe and Canada. All of these reports pre-date the recent news stories regarding Singulair and suicide.

In addition to those reports, the most important thing that I have posted is the reference to the fact that Merck itself recognizes that there are genetics differences among patients that are directly linked to the potential efficacy of Singulair (montelukast). I posted a British reports on that subject and a reference to Merck's clinical trial where they studied genetical differences and montelukast.

The best thing that we can do is to try to convince our doctors that this is not politics -- the major does not have to rule. Why do European countries publish frequent reports on all adverse drugs reactions not just those of the majority of the people? One size does not fit all.

The actual incident of headache in all users according to European reports is 18-19%. So when I read that headache, adverse drug reaction to a leukotriene receptor antagonist (Singulair) is then treated by ibuprofen (a Cox-2 inhibitor), which of course gets treated for stomach inflammation or GERD by Nexium or another drug-histamine receptor antagonist, then I wonder what the hell is left to inhibit? So if a patient does not fit the profile of the 80%, do we have to make that patient catatonic (meant figuratively)? I realize that this leaves out all of the receptors that aren't affected by any of these drugs but I am just trying to make a point.

So why does Merck list headache as just one of the side effects in a category of side effects just listed as greater than 1%? And why do so many people believe that there is no scientific proof of any of the complaints that we see here at this site?

Some of you who are following this site may remember that I posted that when I was following the pathways of the leukeotriene receptor antagonist Singulair that I got to a point where I concluded that there has to be a genetic component (meaning that there are different gene groups of people) and that the efficacy of Singulair (and possibly safety) can vary depending upon what gene group people are in. So I took a little time to see if anybody else was already studying that issue. And YES, they are -- including Merck.

quote:

" However, logically one might predict that it will be the combination of the polymorphisms in these different key regulatory enzymes and receptors that may ultimately determine treatment response. There have been some attempts to tease out the possible contribution of different genes important in this pathway for treatment response to a Cys leukotriene receptor 1 antagonist.18 However, because of the number of potential gene variants that may contribute to efficacy, large studies will be needed to fully evaluate the potential contribution of pharmacogenetic variability in this pathway to treatment response to Cys leukotriene receptor 1 antagonists. Work in the cardiovascular field has demonstrated the potential importance of genetic variants in this pathway to disease risk and also to treatment response,19 suggesting the potential for important effects to be defined in asthma."

(Chest. 2006;130:1873-1878.)
© 2006 American College of Chest Physicians

Pharmacogenetics of Asthma
Ian P. Hall, DM
* From the Division of Therapeutics and Molecular Medicine, University Hospital of Nottingham, Nottingham, UK.
Correspondence to: Ian P. Hall, DM, Division of Therapeutics and Molecular Medicine, University Hospital of Nottingham, Nottingham NG7 2UH, UK; e-mail: Ian.Hall@nottingham.ac.uk

http://www.chestjournal.org/cgi/content/full/130/6/1873

And Merck sponsored a study on this which is now completed.

http://clinicaltrials.gov/ct2/show/NCT00116324?intr=%22Montelukast%22&rank=79

Of course, it was sponsored by Merck and paid for by Merck.

I don't know if the study discovered anything but I believe this is an indication that Merck acknowledges genetic differences in populations that may predict the success of montelukast.

I am not any where close to being an expert in this field. I have another background but I believe that there are experts who can tell you exactly why you had side effects from Singulair.

My opinion:

After many hours of searching scientific databases, I have so far been unable to find any research that has been done on how Singulair (montelukast) affects the brain and brain function. So far, I have also found no funding opportunities for any researchers to study montelukast and the brain. That does not mean that they don't exist, I just haven't located any as of today. I have been to many sites putting montelukast in the search area.

I personally believe that this is a consumer BEWARE situation. I personally would not take this drug after seeing for myself how little we can find out about how it interacts with brain chemicals. The FDA needs to require drug companies to study how medications affect the entire body not just one area. Human beings aren't just a nose and a pair of lungs. And we can't keep going around to different doctors to try to find a fix for a medication that is screwing up other parts of our bodies.

After learning that some researchers in other countries have found leukoteine receptors in the brain of human beings, I find it possible to believe that everyone who takes this medication that suppresses the function of those receptors are in some way being affected by Singulair whether they know it or not. I would want to know that Singulair was studied carefully to show how it affects the brain and what the long term consequences are for those who take it. Until that is done, I believe that consumers should heed the warnings regarding adverse psychiatric drug reactions and consider all of the potential options for safe and effective treatment of their conditions. If Singulair is the best option, then consumers should be told what the risk are and how to handle them.

(I posted this before but after receiving some e-mail, I have revised a few sentences to hopefully make it more understable. )

I would like to share this information with everyone. First, I would like to caution all that it does not prove anything regarding the negative side effect of Singulair but it does suggest that there might (only might) be a physiological cause for any side effect that could be attributed to brain function. A Chinese team has been studying the receptor (Cysteinyl leukotrienes receptor 1) that is targeted by Singulair and is responsible for the method of action that makes Singulair successful. Here is one of their studies.

1: Neurosci Lett. 2004 Jun 17;363(3):247-51. Links Expression of cysteinyl leukotriene receptor 1 in human traumatic brain injury and brain tumors.Zhang WP, Hu H, Zhang L, Ding W, Yao HT, Chen KD, Sheng WW, Chen Z, Wei EQ. Department of Pharmacology, School of Medicine, Zhejiang University, 353, Yan An Road, Hangzhou 310031, PR China. Cysteinyl leukotrienes (CysLTs) are potent proinflammatory mediators. CysLT receptor 1 (CysLT(1)) is one of the two CysLT receptors that has been cloned. Although the expression of CysLT(1) in the brain has been demonstrated by Northern blot and RT-PCR analyses, the location of CysLT(1) in the brain remains unknown. The objective of this study was to examine the distribution of CysLT(1) by immunohistochemical analysis in human brains with traumatic injury or tumors. CysLT(1) was expressed intensely in the microvascular endothelial cells in both normal and abnormal conditions. At 8 days after traumatic injury, microvascular regeneration was found and all of the endothelial cells highly expressed CysLT(1). In gray and white matters of the normal regions of the brain, CysLT(1) was expressed weekly or not at all. However, the CysLT(1) expression increased in the neuron- and glial-appearing cells in gray and white matters after traumatic brain injury. CysLT(1) was also detected in astrocytoma, ganglioglioma and metastatic adenocarcinoma, and the expression in the neuron- and glial-appearing cells around brain tumors increased robustly. PMID: 15182953

Here is the relevant part of the study. "Although the expression of CysLT(1) in the brain has been demonstrated by Northern blot and RT-PCR analyses, the location of CysLT(1) in the brain remains unknown." That sentence says that these scientists believe that CysLT1 exists in the brain but they did not know what the location in the brain was. Then they did this study which showed that the receptor existed in the tissues of the brain that are listed above and are too complicated to discuss here.

It is logical to assume that if a receptor exists in any part of the body that it has a function in other words it does something or tells some other part of the body to do something. They have not proved (that takes many studies) what part of the brain or what the receptor does in the brain or what the effect on the body is if the receptor does not do it's job. We do know that Singular (montelukast, Cysteinyl leukotriene receptor 1 antagonist) blocks this particular receptor so if the receptor exists in the brain that it COULD BE POSSIBLE that Singular prevents this receptor in the brain from doing it's job whatever that is. I know that it is difficult to argue with doctors. This drug has been around a long time. It would be difficult to understand why we are just learning about problems after so long a period of time. I can see from all of these responses that these problems are very real. Of course, we have no idea if Singulair is related or not. But if you need something supportive to show that it is not impossible for them to be related even though there is no proof that they are related, you could print this out and discuss it with your doctor.

This isn't proof of anything but at least it might be a clue. It just shows that it is not impossible that Singular affects brain function in some way.