Leukotriene receptors symptoms and conditions

We have all been saying that our issues regard not being informed about all of the possible side effects. And, we know that Singulair works well for some people. Nobody wants to take a good drug away from those for which it probably performs miracles. People who have toxic side effects have a right to know up front.

My observations about montelukast's chemical structure are either general or not quite 100% correct or could be quite vague - so forgive me. I do not claim to be good at organic chemistry. But from doing a little work, I have come up with some observations.

1. It would seem to me that montelukast might work quite well for people who have developed mold category related asthma. I observed that chloroquinolin, a component of montelukast, is a good fungicide effective against Aspergillus, Alternaria, Cladosporium, Penicillium and Candida. Dust mites can only digest if helped by aspergillus so they go into the mold category. Molds produce millions of spores so anyone who lives in contact with mold would be chronically sick from their presence. Then people get hypersensitized to that.

I am probably wrong but I could imagine that montelukast is: 1) a ligand that binds to an empty cysLT1 receptor for a period of time 2) 7-chloroquinolin-2-yl which either acts intact or breaks down into a quinoline fungicide so that it kills the chronic mold/fungus infection and 3) a sulphur/methyl anti-inflammatory component that tells the t-cells that they are not needed so they will die. Wow, that would be great for mold asthma if it was completely non-toxic. It would be also great under controlled circumstances for many people who are mold-miserable. If I am wrong, I better go out into my garage and start inventing such a drug.

This is my visualization to try to explain the side effects of neurotoxicity. So adverse reactions could be to the quinoline component as an allergic reaction or dose related so that it just built up to a toxic level over time. There are many signs that t-cell populations are significantly reduced by montelukast. The fact that the Italians can do it in the test tube might be that it's a chemical component of montelukast designed to cause the t-cells to die.

Montelukast is a large molecule so Artie says it cannot penetrate the blood brain barrier. That would be an argument if nobody was complaining about neuro-psychiatric side effects. The neuro-psychiatric side effects are identical to quinoline and quinolones. When I read about Lariam, it just sounds like a more extreme version of Singulair side effects. Chloroquinolins were used before they invented Lariam, which is stronger. The malaria Plasmodiums became immune. Hallucinations, anxiety, depression, suicidal thoughts are completely consistent in all of the quinoline/quinolones. If montelukast breaks into sub-molecules then quinolines easily penetrate the blood brain barrier.

I find clinical evidence that montelukast may act as more than more molecule. And, that there is a rational for the existence of the chloroquinolin and evidence that it may be the source of toxicity.

I am glad to risk being called crazy. That is what the internet is for. We can present our ideas and discuss. So, just take this with a grain of salt. If I am close to the truth, this post will find it's proper home.

CysLT1 receptor (the one that Singulair blocks) is also expressed (shows up) in the spleen. I have not seen anything yet that says what it does in the spleen. The spleen has important immune system functions especially in children. It contains B-lymphocytes that fight infection.

: Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:587-97.Links
Cysteinyl leukotriene receptors.Evans JF.
Department of Pharmacology, Merck Research Laboratories, Merck & Co., West Point, PA 19486, USA. jilly_evans@merck.com

The cysteinyl leukotrienes, leukotriene C4 (LTC4), leukotriene D4 (LTD4) and leukotriene E4 (LTE4), activate contractile and inflammatory processes via specific interaction with putative seven transmembrane-spanning receptors that couple to G proteins and subsequent intracellular signaling pathways. Pharmacological characterizations identified at least two subtypes of cysteinyl leukotriene (CysLT) receptor based on agonist and antagonist potency for biological responses. The rank potency of agonist activation for the CysLT1 receptor is LTD4 > LTC4 > LTE4 and for the CysLT2 receptor is LTC4 = LTD4 > LTE4. CysLT1 selective receptor antagonists are efficacious in the treatment of asthma. No selective CysLT2 receptor antagonists have been described. Molecular identification of the human and mouse CysLT1 and CysLT2 receptors has confirmed their structure as putative seven transmembrane domain G protein-coupled receptors and largely confirmed the previous pharmacological characterizations. The CysLT1 receptor is most highly expressed in spleen, peripheral blood leukocytes including eosinophils, and lung smooth muscle cells and interstitial lung macrophages. The CysLT2 receptor is most highly expressed in the heart, adrenal medulla, placenta and peripheral blood leukocytes. The molecular identification of the mouse CysLT1 and CysLT2 receptors show similar but not identical profiles to the orthologous human receptors.

PMID: 12432945

I am starting a new post in the hopes that others will see what I am trying to say about the delayed reaction in those that took Singulair for allergies.

If it is consistent that Singulair does not stop allergy symptoms immediately, then the pathways that eventually stop allergy symptoms involve a change in the mast cell function, development and migration (or some combination).

I asked this question for a reason. Are allergy symptoms stopped immediatedly. My question below:

I have a question that will help me continuing looking for information. I can understand that in the case of asthma that Singulair would provide immediate relief. If it is used for seasonal allergies or other allergies without asthma, does it work right away or does it take a period of days or weeks to be effective? If it takes time, could you tell me how long it took in your situation?

My thinking was going in the right direction if the answer below is consistent of everyone or most.

about 2 hours ago on Apr 11, 2008 by catherineevans, #7045
My granddaughter was put on Singulair for allergy symptoms without asthma. Itching, red eyes, terrible congestion, etc. dark circles under her eyes all the time. When we first put her on this, we didn't see any consistent results for 2-3 weeks, then it seemed to 'kick in.' I don't know if this helps. By the way, she was 9, now she's almost 12 and was immediately taken off when this story came out 2 weeks ago.

Then after seeing one response, I gave my reason for asking.

I asked this question because I have a theory of how montelukast really works for allergies as compared to how it works for asthma.

Asthma is a hyper-sensitive state that gets going because the mast cell has a receptor (the leukotriene receptor that Singulair blocks) that sends a signal along a pathway that causes lung tissue to have that extreme response - the wheezing, the airway constriction.

On the mast cell is another receptor the histamine receptor that causes the secretions that make our noses runs and and stuff up. This is not the same immune response as the asthma response. When I saw a post that somebody's doctor said that Singulair is an anti-histamine, NO it is NOT.

So if Singulair does not block histamine immediately and your child's allergies did not go away immediately, then maybe Singulair is working through some other means such as changing normal mast cell homeostasis.
I know that this seems like "what does this mean?" I am really writing this hoping to God that there are people reading this site that know what I am talking about.

Thank you so much for responding. Your answer actually told me what I wanted to know and confirmed my hypothesis. More answers will help. I hope others respond.

PLEASE respond about the length of time that allergies disappeared if you took Singulair for allergies.

From Canada:

Leukotriene receptor antagonists: suspected adverse reactions

The cysteinyl leukotrienes are inflammatory mediators that bind to cysteinyl leukotriene receptors found in the human airway and cause a number of airway actions including bronchoconstriction, mucous secretion, vascular permeability and eosinophil recruitment.1 Zafirlukast (Accolate®) and montelukast sodium (Singulair®), marketed in Canada since November 1997 and August 1998 respectively, are competitive cysteinyl leukotriene receptor antagonists. Zafirlukast is indicated for the prophylaxis and chronic treatment of asthma in patients 12 years of age and older.2 Montelukast is indicated for the prophylaxis and chronic treatment of asthma, the treatment of asthma in ASA-sensitive patients and the prevention of exercise-induced bronchoconstriction in pediatric patients 6-14 years of age and adults 15 years of age and older.1

As of June 1, 1999, the CADRMP has received 41 reports of suspected adverse drug reactions associated with the use of zafirlukast and 22 associated with the use of montelukast. This article will discuss a serious and rare adverse reaction associated with the use of these agents, drug-drug interactions and unexpected adverse reactions that have been reported to the CADRMP.

http://www.hc-sc.gc.ca/dhp-mps/medeff/bulletin/carn-bcei_v9n4_e.html

Conditions are discussed in the article.

I read these posts and regarding my being quoted as saying that it is unclear whether there are leukotriene receptors in the brain, that isn't true, there are leukotriene receptors in the brain and the relationship between neural systems involved in inflammation and mood is well established. I don't think the misquote was deliberate, I wasnt that definitive when I commented to the reporter on the 'breaking' story (she called me because I had just blogged about it and I updated the blog after I got off the phone). There are a number of parallels with other drugs used to treat medical conditions that have been associated with psychiatric side effects, you can follow the links from the March 27 post "If they dont kill us they will drive us crazy" at
http://www.beforeyoutakethatpill.com/blog.html

Doug Bremner MD

I just want to tell you another thing.

There are leukotriene receptors in the brain" That is the real quote from Dr. Bremner.

When I read that he said "unclear", I said, what?, are these Chinese researchers that have been saying since 2002 or maybe before just "cuckoo"?
So the media deliberately misquoted.

Dr. J. Douglas Bremner's real quote:

There are leukotriene receptors in the brain, and since this drug
binds to this receptor and since depression is mediated through the brain, this suggests a mechanism by which Singulair could cause depression. Could other drugs in this class have similar effects?
The FDA is investigating all of the leukotriene antagonists, probably with good reason.

Thank you Dr. Bremner.

I am not here to promote Dr. Bremner. I will swear that I didn't know about his real quote until less than an hour ago.

I am so pissed. Never trust what you read in the news. I read an article where Dr. Bremner said that it is unclear whether leukotriene receptors exist in the brain. WELL, all researchers know about that word unclear--it has many meanings. It appears in abstracts practically as a BUZZWORD. When I first heard about Singulair and these problems I wanted to know if the leukotriene receptors existed in the brain. Well, lo and beyond, I found researchers who said that they did. Look at the date on this link where Dr. Bremner says that leukotriene receptors exist and look at the date of the article where Dr. Bremner is quoted as saying unclear. WHAT FREAKIN BS. Dr. Bremner says on his website that they exist. Who controls what the media writes? You tell me?

http://www.beforeyoutakethatpill.com/blog.html

I thought everybody would be interested to know about the researcher from Emory that commented on possible psychiatric side effects of Singulair if leukotriene receptors exist in the brain. Here is a description of his book. I hope that we will hear more from Dr. Bremner. And, no I am not here to promote his book. I just saw this today when I was searching for other information. I was thinking about his quote and wanted to know his background.

Merck’s Singulair likely to see prescription drop-off only in high-risk populations
By Beth Herskovits and Gayatri Iyer in New York
Published: March 28 2008 19:52 | Last updated: March 28 2008 19:52
This article is provided to FT.com readers by Pharmawire—a news service focused on providing insight into the most price sensitive issues in the global pharmaceutical market. www.pharmawire.com

"Dr Douglas Bremner, director of Emory’s Clinical Neuroscience Research Unit, noted that drugs can cause psychiatric effects when the targeted receptor also exists in the brain. But he added that it’s unclear whether the brain has leukotriene receptors.
He noted that despite the updated label, the side effects ”sort of flew below the radar.” However, he painted a grimmer picture of the effect on the market, saying this would affect Singular sales badly. People are likely to stop taking it, he added. "

Before You Take that Pill
Why the Drug Industry May Be Bad for Your Health
J. Douglas Bremner - Author Book: Paperback | 8.26 x 5.23in | 448 pages | ISBN 9781583332955 | 28 Feb 2008 | Avery | Adult
A medical expert reveals risks of the most commonly prescribed drugs-and why the drug industry doesn't want consumers to know about them.

Recent scandals involving diabetes drugs, Vioxx, and many other medications reveal the serious and undisclosed risks of some of the most commonly used prescription drugs in this country. In Before You Take That Pill, Dr. J. Douglas Bremner, a researcher and clinician at Emory University whose study on Accutane and depression made headlines, offers an inside look at the pharmaceutical industry, as well as a scientifically backed assessment of the risks of more than three hundred prescribed medications, vitamins, and supplements.

While many drugs are essential to the health of consumers, as Dr. Bremner explains, for many people, the benefits may not outweigh the potential side effects. This book contains warnings that are not on the drug labels. It also exposes tricks of the trade that demonstrate how the profit-making interests of "big pharma" may not always be in line with the safety of the public - from the corruption that exists in the drug approval process to the tactics drug companies use to encourage doctors to prescribe their products. Most important, Before You Take That Pill empowers readers by giving them sound information on specific medications so they can understand and weigh the potential risk themselves. Backed by the latest studies, as well as insight from a doctor who is in the trenches, this book should be on the shelf of every drug consumer.