Blood brain barrier symptoms and conditions

As I read these posts I want to S C R E A M! This drug is like a slow death from Arsenic. If your Memory is impaired, it should be. It's listed as one of the side affects right inside the pamphlet that the Pharmacist gets. I have a Pharmacist friend and she read me, muscle pain, joint pain, muscle twitching and on and on. It's poison for sure and anyone on it should get off it ASAP. My husband's been off for one year next week and he still experiences mental sluggishness and cognitive deficits. So much so, he's retired because he could no longer do his job. It creeps in on you slowly, and insidious. When you start to notice, you're scared to say anything or you don't associate it with this drug. Guess what, the only drug he's ever taken. And, oh yeah, lead to depression. This is a centrally active Ace Inhibitor that cross the blood brain barrier and is literally poisoning you. Actually, there is a derivative from a Brazilian Pit Viper. Synthetic or not, it's poison. Get off people, get off. It will eventually affect your memory more and more until you resemble some form of dementia. Maybe that's why so many people are sitting in Nursing Homes with full blow dementia. The disease that caused it are the DRUGS you're taking.
Get off.

Is anyone experiencing confusion, trouble thinking, trouble concentrating, decreased cognitive function, mental sluggishness, trouble solving problems or situations which require logical thinking and sequencing, and memory loss? Would love to hear from anyone experiencing any these symptoms and if so, how long were you on the drug.
Thanks!

P.S. I just happened to visit the Alzheimers Association Sites Forum as I was interested in a connection between BP meds (particularly this crap) and guess what...you will not believe the those folks diagnosed with Early Onset Alzheimers who have taken Lisinopril for years before diagnosis...Hmmm...any connection here...bet there is...? This crap has been around since the early 80's...wonder how many people now in there 70's were taking Lisinopril in their 50's and are now suffering dementia. This is not coincidence folks. These BP meds that cross the blood brain barrier are doing more harm than good. Can't understand why if this drug can cause depression, it can't be doing other things to the brain. It is...I tell you it is....get off this crap before you're sitting in a Nursing Home and don't know your ass from a hole in the ground.

This drug crosses the blood brain barrier thus the anxiety and depression. It is damaging your brain not to mention all these other ailments. It shrinks the brain and is causing cognitive deficits. All should google the recent article in Sunday paper from the Pittsburgh Post Gazette regarding Mylan Laboratories. Hmmm....maybe this is why so many people are sick from this drug. Here is the website address: *******
I still have tablets although my husband has been off them for 10 months. Guess what...they have a big "M" on them...isn't that interesting. I don't believe a word any doctor or any study has out there on this drug. This drug is tainted with something causing all these issues. This isn't healthy, it's poison straight from a venomous Brazilian pit viper. And if they try to tell you it's the synthetic version...bull crap! It causes the same horrible side affects that over 2500 people have described. I guess WE'RE all nuts and it's not the drugs . Huh!

Hi I am from Nepal, and I am 28 years young, male. I have been taking Lisinopril for about 2 years now. At the beginning this drug seemed to have no side effects at all but as the days progressed I could see the side effects. As side effects started to climb up hill day after day, my friend suggested me to consult my physician immediately. So I consulted my physician yesterday and he told me to do an array of tests; blood test including thyroid hormone test, ECG, and chest X-Ray. My reports will come in due 1 weak time. For now my doctor has changed this medication and given me amlodipine and atenolol combination and its trade name is "amlobet" (manufactured in india by: sun pharmaceutical industries). I took 1 dose yesterday and some of my symptoms seemed to disappear, but I'm quite not sure whether its my Psychology that has contributed to the sudden disappearance of some symptoms or the drug itself. I still have to take this medication for some time to make sure of it.
Some side effects experience during Lisinopril intake:

1. Extreme fatigue and lack of interest in doing day to day work this symptom has disappeared as i started on the new medication.
2. Depression like feeling specially early in the morning and at night times.
3. Waking up in the middle of the night.
4. Vivid dreams.
5. Foggy thinking.
6. Nervousness.
7. Palpitation.
8. Anxiety.
9. Profuse sweating.
10. Shaking of hands and legs during nervousness.
11. Slight Memory loss.
12. Lack of concentration.
13. Mood swing (extreme).
14. Dullness (extreme).

As I progress on this new medication I will update this blog. And I'l also give information regarding my blood tests and ECG tests after my report comes. For now this much. But I recommend Lsinopril users to consult their respective physician seriously before taking this medication and consult even if you are on the medication. This drug seems to pass the blood brain barrier and reach the brain so it affects the central nervous system directly which is not the case in some HBP medications like; amlodipine, atenolol etc.

Just read posts. Will think how to make experience better.

I have taken my three doses within two days, as prescribed so far.
(100mg twice a day).
I may just take one dose today to give my system a reprieve and then think I will stock up on things to help, and go again and try to do the week prescribed.
I AM NOT A DR. so don't take what I Say, as Your authority...but remember that doctors are "practicing" experts at their work" and drug companies like money. Some prescriptions save lives, and others, well...one needs to research and work with or change the method or part of the method. I go herbal whenever possible and hardly take any medications.

My adverse symptoms during this prescription are: Feeling a bit depressed anxious, and withdrawn, almost toward paranoid, Almost. But still ok,"riding the rim" so to speak.
1. "I have heard"... alpha lipoic acid crosses blood brain barrier so that ought to help with brain talking to itself re:
low heavy mood.
Also amino acids, thanks for that too!
2. WATER.
3. Exercise.
4. I think nettle tea as general tonic:
(must boil first for 25 minutes for fresh nettles)
5. I'll get some dandelion root if I don't have milk thistle on hand, or maybe even if I do!
6. I know Omega 3's help with mood
and more so I hope that won't interfere
(does it have minerals???),
I will likely take it anyway between pills.
7. Stay out of sun for now.
8. Vitamin D3.
9. Eat good size meal first.
10. Some Vit. C seems good and also B Vit for stress.
11. Rescue Remedy is a Bach flower remedy for stress. Take as directed, but AGAIN, go slowly if you are listening here, as EVERYONE is different.I take no responsibility for how these things
may effect YOU...but i hope it helps.
One needs to think and trust...
"How do I really feel?" and do the research and look for YOUR options. What works for one doesn't always work for another. I am going to think: what is an immune booster and what is a mood stabilizer, with foods and vitamins, and see if I can keep the prescription going for the week. Coffee~caffeine causes me anxiety. But Turkey has tryptophan in it, that calms.
This is how I NEED,
to THINK...very carefully.
Will call Dr. NOW and let him know what's up for me, and meanwhile, I will try to manage it from info I can muster.
Will see...I don't know outcomes yet, but I do feel, depressed right now.
Stay alert, be gentle and pampering where possible, with my day, calming music, meditate on PEACE...call a friend for temporary support, and do my best.
Here I go....water, big meal, pay attn. to what I need.
CHANGE prescription if too hard!
But...try this way first.
Some people generally absorb meds well and some don't.

I received yet another email from someone who has had a recent MRI due to memory difficulties and the MRI indicated brain shrinkage. This drug is breaking the blood brain barrier, causes depression, and is shrinking the brain. I know of 3 people who began Lisinopril and over a period of less than 2 years, have had MRI and their brains indicate shrinkage. We are wondering why Alzheimers is becoming an epidemic. More people are being prescribed Blood Pressure medicines at earlier ages, particularly Ace Inhibitors because they are cheap and these drugs are pentrating the blood brain barrier and causing a drug induced brain damage that mimicks Alzheimer symptoms. It begins to appear as depression, so, they treat the depression with anti-depressants. They improve for a period of time and then the symptoms of memory loss, difficulty retaining, concentration issues, mental sluggishness begin to present again. The Doctors are in denial, not us who are posting these symptoms. The obvious is oblivious. You cannot take a healthy individual who never took anything more than an aspirin and within 17 month of taking this medication have depression, memory issues and brain shrinkage. I hope if there are any Doctors that read this site, they pay attention to their patients and watch those people on Ace Inhibitors who then follow a pattern of memory problems and depression. It's much more than depression. I bet if all those people who experience memory difficulties got and MRI, there brains would show shrinkage.

My then 11 year old daughter received her first vaccine in June 2007, and third in December 2007. In January 2008, she began complaining of backaches and headaches. During the spring/summer 2008, she began having tremors, tingling and numbness in her legs and arms. She is always tired and never feels good. We have seen a neurologist and 2 neurosurgeons, had CT scans and MRIs. But no answers. She is on medication that has helped slightly, but she still suffers from a constant headache that she never ranks less that 4 on a scale of 1 to 10. Typically she rates it as a 7 or 8, and we have had a couple of 12s.

Is anyone experiencing confusion, trouble thinking, trouble concentrating, decreased cognitive function, mental sluggishness, trouble solving problems or situations which require logical thinking and sequencing, and memory loss? Would love to hear from anyone experiencing any these symptoms and if so, how long were you on the drug.
Thanks!

I am 34 years old. I am a pharmacy tech. I have asthma and allergies. I have taken singulair pretty much every day since it came out on the market. I've had asthma since i was about 10 years old. I took theophylline as a kid. Steriods on and off especially during times when my allergies are bad. I still use Advair during the fall and spring. Every drug has a side effect. However breathing is pretty good damn thing. Do I have days when I feel low? Yeah. Do I sometimes have nightmares? Yup. Are "natural" products the answer. Not always. The fish oil that some of the posters are touting can also cause GI problems. Some of the natural products contain herbs and other plant derivatives that can be harmful for a child that suffers from allergies. Not proactively treating asthma can be deadly. Some of the parents are suggesting steriods as the answer - those can cause weight gain, growth suppression and can lead to a worsening of asthma.

Singulair has never made me feel like I've wanted to kill myself. I was more depressed and angry as kid when my asthma did not allow me to partipate in normal childhood things. I was sad and hated life when I couldn't keep up with friends at recces because I was having trouble breathing. You have to outweigh the costs with the benefits. I am more irritable when I have asthma flareup then I am on a normal day. For me, I choose to breathe. And singulair has been helping me for almost a decade.

I'm not saying the medication isn't causing these symptoms but maybe there is an underlying cause to your child's depression.

Any drug has a side effect. But without medical research and the medications that come with them - people would still be dying of simple diseases and we wouldn't have vaccinations. As a society, as a whole, we are a culture that looks to someone else to fix things and then blames the people who try to fix it. We need to stop being the "hot McDonald's coffee'" society.

Well, I beg to differ with "huh1051" regarding the snake venom. This is straight from "Wikipedia"... History/brand names
Lisinopril was developed by Merck & Co. and is marketed worldwide as Prinivil or Tensopril and by AstraZeneca as Zestril. In India it is marketed by Micro Labs as Hipril. In the United States, a generic version is available. Like other ACE inhibitors, it is derived from the venom of the jararaca, a Brazilian pit viper (Bothrops jararaca). So, "what" do you believe!!!???? This drug breaks the blood brain barrier which is probably why so many people get depression. However, I "think" this drug is causing more than just depression. It's shrinking the brain and affecting memory.
bellabear

Why does Singulair cause these symptoms? I am going to give my explanation which is only a HYPOTHESIS. This should not be categorized as any thing but an educated guess. This is not backed by scientific research because nobody will do any research that would appear to anger
Merck even if people are suffering in the thousands.

1. The original research that preceded the development of Singulair (montelukast) seemed to focus on the theory that asthma was caused by an unusual immune response to certain pathological stimulus. There are many references to the observation that a high percentage of asthma sufferers are people whose asthma is caused by fungus. Many people suffer from asthma and are told that they are allergic to dust mites. Dust mites can live only because the fungus aspergillus pre-digests the
food source that dust mites can then absorb. Other sources of fungus occur in the home due to dampness or problems with wood rot.

2. The body's immune system fights certain categories of pathogens such as bacteria and fungus by creating nitric oxide which kills them at the site where they try to enter the body. The mast cell is the immune cell that is responsible for the production of nitric oxide. Mast cells are found in the skin, airways, intestines etc. The mast cell is capable of many different types of biochemical functions that are designed to signal other cells or other chemical responses. When the mast cell knows that pathogens
are present and nitric oxide is NOT produced, then it signals other immune cells to be sent to the site of the infection. Thus in the case of asthma, it is known that excessive numbers of eosinophils appear in the airways and these cells create inflammation.

3. Singulair was developed for asthma and later allowed to be prescribed for other reasons. I believe that montelukast probably creates a source of nitric oxide that prevents the mast cell from signalling for other immune cells to arrive at the source of infection. I arrived at that conclusion from studying the chemical structure of montelukast, the chemical structure of the gene cysLT1 receptor, and the chemical structure of the cell wall of fungus which would be what the mast cell uses to determine "what to do in order to kill the fungus."

The researchers who invented montelukast first had to clone the gene-cysLT1 receptor meaning that they had to be able to identify the gene and replicate it. Then by trial and error they had a find a "chemical"
that would bind (connect chemically) to the cysLT1 receptor. The theory would be that montelukast would take the place of the fungus or other pathogen and thus prevent the gene from reacting to produce the
responses that the sick patient with asthma produced. Merck says in the literature that montelukast binds with the cysLT1 receptor in order to prevent the mast cell from signalling the eosinophils to arrive in excessive
numbers that cause inflammation. I believe that montelukast is also causing the production of an amount of nitric oxide that is actually killing the pathogens that are present. For one thing, I would think that it
would be dangerous to incapacitate the immune system in that way without providing a way to kill the pathogens. I don't believe that the asthma response is just allergies to something like dust. Pollen from trees and flowers is loaded with fungus spores.

4. IF, IF, IF, montelukast does actually produce nitric oxide, then it does so by binding with the gene. Any place in the body where a molecule of montelukast encounters the cysLT1 receptor (a gene) then the corresponding molecules of nitric oxide are produced before the liver enzymes break the montelukast molecules up. Nitric oxide is TOXIC and
INFLAMMATORY. So let's look at the symptoms in regard to the location of the cysLT1 receptors. The location of these symptoms would not be places in the body where the mast cells normally encounter fungus or bacteria. The cysLT1 also has other functions in that it communicates with the cysLT2 receptors. Obviously, nitric oxide
should not be produced in these locations because of the signalling effect of nitric oxide on other physiological functions.

a. intestinal pain - the cysLT1 receptors are located in the small intestines
b. leg pain actually caused by vasculitis - cysLT1 receptors are found inside blood vessels- consistent with the fact that montelukast causes
Churg-Strauss
c. some people who didn't have asthma develop asthma - the cysLT1 receptors are in the airways
d. nightmares, depression, neurological damage - when montelukast penetrates the blood brain barrier probably due to unusual conditions of blood pH or electrolyte imbalance then nitric oxide in the brain causes neuron damage and excitoxicity

5. Why do some patients not experience side effects? Probably because genetically they are completely compatible with the model that researchers created when they cloned the cysLT1 receptor gene. I didn't not find any information about whether researchers knew that there are many different variations of this gene.

6. IF, my theory is even close to being correct, then why doesn't Merck do anything about researching these side effects. Maybe because nobody in the company knows how this drug works but the researchers who created it. All of the Merck literature is very vague about any biochemical information.

Again, this is just speculation and hypothesis. I have made an attempt to put this in simplistic language and therefore sacrifice scientific accuracy. But, I think that you will get the point.

SINGULAIR IS VERY DANGEROUS TO PATIENTS WHO EXPERIENCE NEGATIVE SIDE EFFECTS. DOCTORS SHOULD JUST REALIZE THAT
THOSE PATIENTS ARE NOT COMPATIBLE WITH THE MODEL FOR THE DRUG.

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.

My 21 yo son started Singulair Aug.5 on Aug 6 he experienced an opthalmic migraine with persistent visual deficits that are constant. He only had one dose. He has never had any type of migraine before or even frequent headaches. Two neuro-ophthalmologists feel he is that rare case his vision may never be normal again. Singulair induced????

My son, who just turned 14 this month, was on Singulair for over 2 years.
He was diagnosed with reactive airway disease and possibly Asthma--and prescribed this awful drug-even back in 2004. The doctor said how wonderful this med was and prevents any further attacks.. So, for 2 years-every night, he took this mood altering, destructive drug. He lost all interest in school, his athletics-soccer, skateboarding, biking..in fact became almost a vacant , very unhappy, child-had stomach aches, joint pains and reflux--why--I brought him to the doctor and Pediatric center so frequently--all they kept saying his --his asthma is better, much be other issues...Even after the March 2008 suicide--his doctor said-that is just an isolated incident-just monitor him--It is a good drug. Right, month by month his behavior escalated to wanting to die, no reason to go to school-he said he was stupid and a failure and why don't I understand there is no reason to his life. A usually happy fun-loving boy -my son- didn't want to live. Nothing made him happy-I started to believe what the doctors said--maybe something or someone at school (bully, pedophile??) caused this change. Terrible nightmares and vivid dreams...Until this past July, I asked him want to go to the library for some books or dvd's...he went ballistic-threw everything off his computer desk and tried to break his chair. He is not an aggressive boy but this behavior was becoming a daily issue. Along with everything flying off his table, was his bottle of Singulair pills. It then dawned on me..I have been poisoning my only son. The child I know and love and gave birth to returned within a few days--although I am worried sick about further asthma attacks --all the doctors can prescribe is a steroid drug-asthmex or Pulmicort.. I cannot understand nor comprehend why this drug is being prescribed for children and young adults. The guilt I live with is terrible as my son has lost 2 years of his life--
and thought there was something really wrong with him-At least we woke up---in time--how about some other parents..thinking it's just normal adolescent behavior for their child or their fault???

This testimony should help strengthen our case for warnings for Singulair.

Neurologist Sought Warning for Pfizer Drug
By JEREMY SINGER-VINE
June 20, 2008; Page B10

A British neurologist who analyzed effects of the drug Neurontin told a court hearing Thursday that he advised its maker -- now a unit of Pfizer Inc. -- to include a warning on the drug's label for potential side effects of depression and aggression, but his advice wasn't followed.

The University of London neurologist, Michael R. Trimble, was testifying at a hearing to decide whether civil cases brought against Pfizer alleging suicides linked to Neurontin can proceed. The hearing was jointly held by judges for U.S. District Court in Boston and a New York state court who are hearing similar cases. In various lawsuits consolidated in the federal court, plaintiffs allege more than 100 suicides were connected to Neurontin usage.

Dr. Trimble described what he said was a "plausible biological pathway" that could lead from the compound gabapentin -- the chemical name for Neurontin -- to suicidal behavior, hostility, and aggression. Dr. Trimble said that in 1995 and 1996, he was hired to write two confidential reports for Parke-Davis -- now a unit of Pfizer -- because the company "was concerned about psychosis in relation to their drug." Dr. Trimble said he was unable to find a link to psychosis, but noted effects of depression and aggression.

Lawyers for Pfizer argued at the hearing that the evidence linking the drug to suicidal side effects wasn't scientifically sound. Under cross-examination, they challenged his description of a pathway as a patchwork of studies that didn't prove a biological connection. Neurontin and generic forms of gabapentin are approved for treating epileptic convulsions, but have also been prescribed widely "off label" for other conditions.

In five of nine patient cases he analyzed in 1996, Dr. Trimble said he saw depression and aggression in patients who had no previous symptoms of the side effects, so he said he recommended to the company that the drug "should carry some kind of warning" for susceptible patients.

Thursday's proceedings were the initial phase of a hearing requested by Pfizer to challenge the opinions of the plaintiffs' experts. Under cross-examination and a subsequent examination by the plaintiffs' attorney, Dr. Trimble said the biological pathway between Pfizer's Neurontin and suicidal events were plausible and supported by a series of peer-reviewed neurology research.

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

My nephew is 7 and has been on Singulair for probably 4 years. His symptoms developed over time but recently have exploded. He has epilepsy so most of the things that he has experienced has been blamed on that. However, today his doctor took him off singulair and said he believes his symptoms are caused from the drug. He started having head drop seizures, fell out of his desk and cut his face one day. He has also been depressed, had severe anxiety attacks for the past 8 months. Several months ago, he started having such severe nightmares that it is almost impossible to get him to go to bed and go to sleep. Recently he began "seeing dead people" and "monsters" that we trying to kill him even when he was awake. He has also cried many nights with leg cramps and severe stomach pain. I will update this page in two - three weeks to let you know if these problems go away now that we have stopped the singulair.

For those people with gastro-intestinal side effects, there is a cysLT1 receptor in gastro-intestinal mucosa - at least in rats, there is. Now, Merck cannot claim the blood-brain barrier on this one. We need to know how montelukast affects these gastro-intestinal receptors (if present in humans) for those people on montelukast long term.

This study in rats suggests that montelukast does possibly (if proven in humans) interact with the cysLT1(singulair) receptor in gastro-intestinal mucosa. How? Good under what circumstance? Bad under what circumstance?

Prostaglandins Leukot Essent Fatty Acids. 2008 Mar;78(3):189-97. Epub 2008 Apr 1. Links
Leukotriene D4 receptor antagonist montelukast alleviates water avoidance stress-induced degeneration of the gastrointestinal mucosa.Ersoy Y, Cikler E, Cetinel S, Sener G, Ercan F.
Department of Histology and Embryology, School of Medicine, Marmara University, 34668 Istanbul, Turkey.

We investigated the role of montelukast (ML), a cysteinyl leukotriene-1 receptor antagonist, on the water avoidance stress (WAS)-induced degeneration of the rat gastric, ileal and colonic mucosa. One group of Wistar albino rats were exposed to chronic WAS (WAS group) 2h daily for 5 days. Another group was administered ML (10mg/kg; i.p.; WAS+ML group) following every WAS exposure for 5 days. Control rats were injected with the vehicle solution only. The stomach, ileum and colon were dissected and investigated for histopathological changes with a light microscope as well as for topographical changes with a scanning electron microscope. The levels of malondialdehyde (MDA, a biomarker of oxidative damage) and glutathione (GSH, a biomarker of protective oxidative injury) were also determined in all dissected tissues. In the WAS group, the stomach epithelium showed ulceration in some areas, dilatations of the gastric glands, degeneration of gastric glandular cells, and prominent congestion of the capillaries. In a similar fashion, degenerated epithelium and severe vascular congestions were observed in the ileum and colon. In all the tissues dense inflammatory cell infiltration and mast cell degranulation in mucosa were observed. The levels of MDA were significantly increased whereas those of GSH were significantly decreased in all test tissues in the WAS group compared to the control group. The morphology of gastric, ileal and colonic mucosa in WAS+ML group showed a significant amelioration showing a reduction in inflammatory cell infiltration and mast cell degranulation. Increased MDA and decreased GSH levels in the WAS group were also ameliorated with ML treatment. Based on the results, ML supplement seems attenuated inflammatory effects of WAS induction in gastrointestinal mucosa.

PMID: 18387287

I don't work for another pharmaceutical company. I don't have any competing interests. People keep asking me that. Why? Is everything about competition and money? I am getting sick of being asked that.

Frankly, I don't see how anybody could go up against all of the high powered lawyers that Merck can hire. If anybody wanted to speak about how this could happen, Merck would have people going through their doctoral dissertations looking for plagerism. Plaintiffs would have Merck detectives outside their houses hiding in the bushes. Merck private detectives would interview their friends and teachers.

All I wanted to do was to show parents and patients that they are not the only complaints. These complaints have been reported before. Whether they resulted in any serious warnings to Merck doesn't really make a difference because people know how they feel or how their child feels on Singulair.

There is nothing that we can do, in my opinion, but to believe in ourselves. We might trying writing to Queen Beatrix of the Netherlands that the American sufferers must have Dutch brains--which allow montelukast to penetrate the blood brain barrier and can she do anything for us? This is ridiculous that we should be getting these responses from doctors.

From the Netherlands 2006.
In three of the cases a positive dechallenge was seen.The fact that the patients (except for one) did not suffer from depressive symptoms before they started montelukast, the short latency, and recovery after withdrawal of the drug all strengthen our hypothesis that depressive symptoms are an ADR related to the use of montelukast. According to the Marketing Authorisation Holder of montelukast, depression will be added to the product information.

Mechanism: The mechanism of montelukast-induced depressive symptoms is unknown. However, montelukast has earlier been associated with adverse drug reactions such as abnormal dreaming, nightmares, hallucinations, agitation with aggressive behavior, irritability and restlessness, which suggests that montelukast can penetrate the blood brain barrier and exert an effect in the brain .

http://www.lareb.nl/documents/kwb_2006_4_montel.pdf.

I was just asked by Dr. ???, if these European reports lead to change in product information in these countries. I did post that I thought that we should try to find that out. I don't have access to that information. But I do see that the Netherlands did require that depression be added to the product information. It doesn't say the date but Merck agreed.

Artie wanted to tell us about the blood brain barrier. Where are you Artie?

The report says:

In three of the cases a positive dechallenge was seen.The fact that the patients (except for one) did not suffer from depressive symptoms before they started montelukast, the short latency, and recovery after withdrawal of the drug all strengthen our hypothesis that depressive symptoms are an ADR related to the use of montelukast. According to the Marketing Authorisation Holder of montelukast, depression will be added to the product information.

Mechanism: The mechanism of montelukast-induced depressive symptoms is unknown. However, montelukast has earlier been associated with adverse drug reactions such as abnormal dreaming, nightmares, hallucinations, agitation with aggressive behavior, irritability and restlessness, which suggests that montelukast can penetrate the blood brain barrier and exert an effect in the brain .

From the Netherlands 2006.

This is the html version of the file http://www.lareb.nl/documents/kwb_2006_4_montel.pdf.

Page 1
Nederlands Bijwerkingen Centrum LarebMei 2007Montelukast and depressive symptomsIntroductionMontelukast (Singulair®)is a leukotriene receptor antagonist available on the Dutchmarket since 1998. It is indicated for the treatment ofasthma as combination therapy forpatients with light to moderate forms of chronic asthma which cannot be adequately controlledby inhalation corticosteroids and short-acting ß-agonists. For asthma patients for whommontelukast is indicated as asthma treatment it can also relieve symptoms of seasonal allergicrhinitis. Montelukast is also indicated in asthma prevention, if exercise-inducedbronchoconstriction is the main factor

Reports On September 20, 2006 the database of the Netherlands Pharmacovigilance Centre Lareb contained four reports of depressive reactions associated with theuse of montelukast.Patient A is a female aged 55 who used montelukast 10 mg once daily for asthma associated with COPD. Concomitant medication included ipratropiumbromideinhalation, salmeterol inhalation, fluticasone inhalation, acetylcysteine, budesonide nose spray and desloratadine. Two weeks after montelukast therapy was initiated the patient experienced nightmares, a depressive symptoms, fatigue and increased dyspnoea. When montelukast was withdrawn, the first three symptoms resolved. It is not known if the dyspnoea resolved. The reporting pneumonologist stated that the increased dyspnoea also could be a sign of progressing COPD. Patient B, reported by a pneumonologist, is a female aged 39 who used montelukast 10 mg once daily for asthma. Concomitant medication included salmeterol/fluticasone inhalation, mebeverine and psyllium seed. One week afterstarting montelukast treatment the patient experienced chest discomfort, malaise,depressive symptoms and dizziness. Montelukast was withdrawn, patient outcomeis unknown. Patient C, reported by a pharmacist, is a male aged 46 who used montelukast 10mg once daily for asthma. Concomitant medication included omeprazole,salbutamol inhalation and budesonide/formoterol inhalation. Six days after starting montelukast treatment the patient got in a depressed state. The patient continued to use montelukast for four weeks but the depression did not resolve. When montelukast was withdrawn, the patient recovered. Patient D, reported by a pharmacist, is a female aged 59 who used montelukast 10mg once daily for mild to moderate asthma. Concomitant medication included mometasone nose spray, salmeterol/fluticason inhalation, oxazepam and paroxetine. Three days after starting treatment with montelukast the patient experienced insomnia and aggravation of her depression. When montelukast was withdrawn the symptoms resolved.

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Nederlands Bijwerkingen Centrum LarebMei 2007 Other sources of information drugs are known to cause depressive symptoms. However montelukasthas not been associated with depressive symptoms earlier . A Medline searchbased on the MeSH terms montelukast, leukotriens, depressive disorder and mood disorders did not yield any relevant publication. DatabasesOn September 20, 2006 the database of the Netherlands Pharmacovigilance Centre Lareb contained four reports of depression associated with the use ofmontelukast (ROR 2.1 95% CI 0.8 - 5.7). The same day the database of the WHO contained 3466 reports on montelukast, 43 of these concerned depression (ROR1.2 95% CI 0.9 – 1.6)MechanismThe mechanism of montelukast-induced depressive symptoms is unknown.However montelukast has earlier been associated with adverse drug reactions such as abnormal dreaming, nightmares, hallucinations, agitation with aggressive behavior, irritability and restlessness, which suggests that montelukast can penetrate the blood brain barrier and exert an effect in the brain .Discussion and conclusionLareb received four reports of depressive symptoms in patients using montelukast.Possible confounding includes that asthma itself has been associated with the development of depression . Inhalated corticosteroids can also exert effects onthe central nervous system. Fluticason in combination with salmeterol which isused by patients A, B and D, is associated with hyperactivity and irritability where as budesonide, which is used by patient C also has been associated with depression . The latency of montelukast-induced depressive symptoms variesfrom 3-14 days. In three of the cases a positive dechallenge was seen.The fact that the patients (except for one) did not suffer from depressive symptomsbefore they started montelukast, the short latency, and recovery after withdrawal ofthe drug all strengthen our hypothesis that depressive symptoms are an ADRrelated to the use of montelukast. According to the Marketing Authorisation Holderof montelukast, depression will be added to the product information.

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'm a 54 year old female. I was given Doxycycline to help treat what may be Interstitial Cystitis - bladder inflamation of unknown origin. Within 20 minutes of taking, I felt like it crossed the blood-brain barrier. I would get a weird dizzy/nausea sensation. I only took it for 10 days and I was so glad to be done as I hated how I felt while on it. What I'm worried about now and this is why I wound up on this site, is that it feels like it is still in my system a week after finishing it. After every meal, my stomach hurts. I've been having headaches --which I don't typically have. I'm having trouble concentrating and focusing on work that I have to do and feeling suddenly sleepy for no good reason. I struggled for years with depression, but have felt relatively good for the last 10 years--I never took any depression meds. Since taking this drug, I have sensations of sadness and hopelessness like I haven't felt in years. I'm worried about the time it's taking for this drug to leave my system and whether it's done some kind of permanent damage.