Metabolite symptoms and conditions

I have been on Ortho-Tri Cyclen lo for about 5 years off an on. When I first started the pill I was fine but after being on it for about a year everything changed. Before I started the pill I was losing weight. I was 163lbs and I got down to about 142lbs which was great but since then I've been on constant weight gain, I've tried metabolite and aerobics, some diet changes and now I last weighed 187lbs, with a few drastic changes I think I've dropped about 3 lbs since then. My sex drive used to be fairly high now it doesn't exist, I'm moody and always have headaches. I get nauseous a lot. So as of today I'm just going to quit the pill and live with cramps.

Everybody here knows that I have been interested in trying to find out if Singulair (montelukast), which is a quinoline, ionizes and forms quinolinic acid under physiological conditions that lower blood pH. Some researchers have also mentioned that another montelukast metabolite that occurs is known to be a toxin. In other words, until someone can get blood tests that confirm what the toxic metabolic is, we are just guessing but I would bet that it is a good guess.

One of the strongest cases for that argument would be what happens to some people during sleep. There are some people whose CO2 levels rise. If the levels rise enough to cause change in pH to a more acid condition, then montelukast can possibly ionizes just enough to create minute amounts of neurotoxins that could cause bad dreams, hallucinations, sleep deprivation or a number of other neuro-psychiatric problems. Compound the effect of night after night of minute amounts of neurotoxins caused by CO2 and montelukast ionization then it would be easy to understand how depression and personality change results. There are other conditions that cause elevated CO2 levels and acidosis such as COPD.

If anyone has any data regarding their CO2 levels from sleep studies or other bloods tests, would you please send me a private message?

Singulair/Quinolinic acid - skin conditions and myalgia caused by eosinophils

Dear friends for this one I feel like Gomer Pyle "well g-o-o-l-l-l-y." I have been trying to solve the riddle as to whether Singulair might possibly cause skin conditions and myalgia. I found where a researcher actually injected himself with quinolinic acid to see if it caused a reaction from eosoniphils. So hypothetically if there were less than ideal metabolic or genetic conditions that cause the montelukast molecule to break up into a quinolinic acid by-product before it reached the liver then eosinophils will go to where-ever the quinolinic acid is. In the case of this researcher, the quinolinic acid caused skin inflamation conditions because he injected it into his arm.

This study could apply to any quinoline type drug that could break down into quinolinic acid. Now, we don't have proof whether Singulair can break down into quinolinic acid so the doctors won't buy this one as a fact. It is good, however, for a WHAT IF argument for those who would like to do a wait and see if Singulair caused the problem. This researchers eosinophil count took five weeks to drop back down to normal levels.

Clin Exp Med. 2006 Jun ;6 (2):60-4 16820992 (P,S,E,B) Is the L-tryptophan metabolite quinolinic acid responsible for eosinophilic fasciitis?

R Noakes, L Spelman, R Williamson
Qld Skin and Cancer Foundation, Greenslopes Private Hospital, Newdegate St, Greenslopes 4120, Qld, Australia. rnoakes@lagunacom.com.au
The eosinophilia-myalgia syndrome is accompanied by alterations in L-tryptophan metabolism with elevated levels of L-kynurenine and quinolinic acid having been recorded. It has been suggested that this is due to activation of indoleamine 2,3-dioxygenase by interferon-gamma. It is unknown whether these products of tryptophan metabolism play a role in the pathogenesis of this syndrome and the closely related condition of eosinophilic fasciitis. To explore this possibility, the principal author (RN) received a series of subcutaneous injections of quinolinic acid. A total of 1200 mg was administered over a 1-month period. Peripheral blood eosinophil counts were monitored and biopsies taken for H&E and immunohistochemical stains. Over the 1-month period the eosinophil count rose from 0.3x10(9)/l to 0.8x10(9)/l before falling to 0.4x10(9)/l approximately 5 weeks later. H&E sections showed a mixed infiltrate of eosinophils and neutrophils extending through the reticular dermis and septa of the panniculus. No deep fascia was obtained on biopsy. The immunohistochemical stain for transforming growth factor beta 1 showed staining of endothelial cells and dendritic cells. The interleukin-5 stain was negative. Our results suggest that quinolinic acid may play a role in cutaneous eosinophilic disorders.

I am posting the metabolism profile for montelukast. Maybe someone here has chemist friends who might know if it is possible that the dicarboxylic acid major metabolite could also have been derived from quinolinic acid under metabolic circumstances less than ideal. The quinoline ring, is a benzene-pyridine. Quinolinic acid, a dicarboxylic acid with a pyridine is produced by the oxidation of quinoline possibly by acid hydrogen peroxide. So the only structural difference between the dicarboxylic acid mentioned in the study as the major metabolite and quinolinic acid is nitrogen. Fascinating drug Singulair. Macrophages (immune cells) make quinolinic acid and release nitric oxide in order to kill micro-organisms. Quinolinic acid a neurotoxin.

Unless you are someone who plans to get help from experts, I would ignore this post. In my opinion, the only way that real answers will come from the investigation is that there is a provable chemical reason that the brain is affected by Singulair. I just post what I find and hope that eventually there will be experts who can explain why people are having such problems. I am unable to draw any conclusions from the report below.

dmd.aspetjournals.org/.../1/1996&journalcode=dmd