May 7th
2008
4:16 PM
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.
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It is well known that quinoline rings can be toxic to some people even very rapidly. As in this very extreme example.
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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.
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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?
-- By concernedcitizen | Reply | (11) replies | Private Message me
April 12th
2008
10:45 PM
I am posting an update on my granddaughterwho has been off for 2 weeks since the story broke in the news. There certainly has been a difference, she's more 'present' when I'm speaking with her, not angry, calmer and she slept through the night the other day when she came over to visit. There were actually no 'scenes' or carrying on. However, in light of the last posting I do not know how she will be affected in the long term, None of us can know that, none of us know how this drug actually works on the brain to create such side effects. I just saw a Singulair commercial on TV and almost got sick. Cody Miller's mom in her post stated that he had no behavioral problems before his death. I imagine that is true for the majority of us. My granddaughter never had the need to go see a counselor before this drug. She was a happy, normal 9-year old. That all changed in only 2 months as her mother took her to a psychologist to find out why she was acting so bizarrely. I am convinced this drug has caused untold misery and should be at least restricted to adults or at most taken off the market. This website is only the beginning at some point those who feel strongly will have to come together and organize against this giant company Merck.
-- By catherineevans | Reply | (3) replies | Private Message me
April 9th
2008
9:52 AM
Hi to all,
I am Cody Miller's mom, the boy who took his life after 17 days on SINGULAIR.I am just checking back to read some postings and I am truly amazed and saddened at the stories.I believe that if you follow through by filing your side effects with the FDA , advise anyone you know to do the same,the seriousness of this drugs danger cannot be hidden or ignored any longer.We have met with some knowledgable people on the drug company Mercks outlandish ,irresponsible practices .They said, the thing that helps in cases like this are,< REPORTS AND PHONE CALLS TO THE FDA>This is what we are being told.I have copied the pages on this website and, the Congresswomans that is helping us, has scanned your stories to disk.We will be taking them to Washington DC on May 2 to speak to the FDA.These stories cannot be ignored.Please make sure you look at all the serious side effects. When speaking to your doctor, let them know that this drug can cause alot of things besides suicide, although that is a serious added side effect. It can slowly steal the quality of your childs life and your family's life.Risk to benefit is all I am reminding everyone of,it seems the doctors sometimes dont look at the overall picture.I do believe however that more physicians are looking at this with eyes wide open, now that people are putting two and two together.My quest is relabeling this drug ,after removing it from the market to study further.Safety should be first ,not profit for GIANT PHARMECUETICAL COMPANIES.Your voices will be heard if you just make waves , have some faith.My husband and I will make it known to all who will listen, we are not alone in our request. They must seriously evaluate this drug and it's benefit to risk ratio, childrens lives are dependent on this important investigation.You can find the phone number to the FDA on the website if this number does not work,718-340-7000ext.5657 Alice in Jamaica New York.This person will direct you if your having difficulty filing on medwatch.com.She will file while on the phone with you.Please again, take these steps to move this important matter forward in the right direction.Blessings to all Kate Miller
September 1th
2008
1:27 PM
I just read the new article about Cody Miller and Dr. Douglas Briggs, who was taking Neurontin. That further confirms the work that I was doing to collect research regarding problems with GABA and suicide. How these drugs affect the brain chemicals is very complicated. I believe that the pharmaceutical companies do know that it is possible for a series of things to go wrong and create terrible adverse side effects in some people - not all.
I will be extremely disappointed if the FDA allows these companies to sweep this under the rug.
Suicide risks studied in drugs for physical ills
By RICARDO ALONSO-ZALDIVAR – 1 day ago
WASHINGTON (AP) — Cody Miller was a high school football player who was allergic to ragweed. Douglas Briggs was a doctor coping with pain from an old back injury.
Both are now dead, hanging victims driven to suicide, their families believe, when drugs prescribed to relieve physical symptoms upset their mental and emotional balance.
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This testimony should help strengthen our case for warnings for Singulair.
-- By concernedcitizen | Reply | Private Message meNeurologist 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.