Singulair side effects

hi,

My three year old son was prescribed singulair - he stopped sleeping well- and started stuttering severely. He had total meltdowns, the like of which,
i'd never seen before. We took him off the medications and the meltdowns disappeared, he started sleeping well again. The stuttering improved but he still has a mild amount of stuttering that we are treating preventatively.

My son has been taking Singular as well as Advair and Zyrtec and Nasonix for the past 6 months. He is doing so well. He has not had to go to emergency, he has not been sick, and he has not had mood swings. If you look at the prescription information that comes with Singular, you can see what the side effects can be. My recommendation is to take your child off of them if they have a side effect. I contacted my Dr. and Merck is studying only 1 case with a child that had side effects, but they did not say if this child was on other Psych medicine at the same time. The 2 psych meds that have shown a bad interaction with Singular are Phenobarbital and Rifanpin (spelling may be wrong). With all the posts I have read, very few people indicate if they are taking other medications at the same time as Singular. My suggestion is that you consult your Dr. and then send your case to Merck for more studies. If all you are doing is posting on the web, you are not solving this issue with the makers of the medication.

Dear Friends,

Just want to reconfirm that this drug, that according to the Lab, present this side effects as "rarely" now we can see that it is not, I have a 2.5 year old boy, that is presenting these same side effects that you are mentioning. In a sudden he starts to act really nervous, his eyes turn red and cries while he tries to express something, but he does not know what is going on, in the meantime he has this truly visible crisis, his heartbeat goes up like hell, and his hands shakes. My wife and I got really scared the first time we experienced this with him, and we did not know what to think, we asked the Doctor and the stupid guy told us that he needed a shrink, but we did not believed it. Today he had the second same crisis, not as hard as the last one, and we discussed and came up with the idea to find out what were the side effects of this drug, and voila, is the gdm Singulair. I just can't believe that the Doctors that are prescribing these drugs do not warn the people that this may happen. The only thing that I can do is write my experience to you, thanking you for your attention, and spread the voice to the other parents that are around me that they take care of this and prevent their children to go through this process. I really feel like trash, because I did not do this before starting giving him this drug. Thanks for listening.
By the way this is an international problem, I am writing you from Mexico City.

I am not sure if my side effect is from using Singulair or not. I just started taking the Singulair 10mg last Thursday only in the evenings. After 3 days my face was swollen to the point that I couldn't see. I went back to the doctor and he didn't think the Singulair had anything to do with it since he was treating me for a contact dermatitis chemical burn so I still continue to take the Singulair but the swelling hasn't gone away yet and it has been 3 more days. If anyone can shed some light on if this is a side effect from using Singulair it would be appreciated. I also am taking Xyzal in the mornings so therefore I am not sure if this is what caused my face to swell. Any replies would be appreciated.

My 8-year-old son started on Singulair 6 weeks ago. Soon afterwards he had severe problems falling asleep--often up until 4 or 5 am before drifting off, but I didn't make the connection. (Thank goodness it's summer time and no school!)

About 2 weeks ago, my doctor recommended Singulair for me, too. The first day I was unbelievably sleepy, but after that I, too, have had severe problems with insomnia. I have also noticed involuntary muscle twitching, restless leg syndrome, and my mind feels like it's turning to mush. I used to tutor statistics; now I can't even do basic multiplication! Scary!

I have just thrown out both my son's and my bottle of Singulair. I hope stopping it will reverse this crap.

I've been on Singulair for more than a few years now. I'm 43, with exercise and allergy induced asthma.....but mild. I also have VERY bad allergies. Talk about being allergic to EVERYTHING outside....that's me. I also suffer from migraines and depression. I've been on every antidepressant out there....still depressed. Now I know why...Singulair. I've tried tons of migraine meds....and I'm wondering if some of my side effects are really from Singulair. I'm moody, I don't care about other people's feelings like I used to, I snap at my kids like crazy,I cry at the drop of a hat....at stupid stuff. And now I'm thinking that my joint pain in my hips is from Singulair. But Singulair was my miracle drug for my asthma and a huge help to my Allegra D for my allergies. I'm asking the doc for an alturnative drug. As soon as I get it I'm off Singulair. ADIOS!

My 16 year old son took Singular for three days. Almost immediately after taking the first dose, he starting having increased blood pressure, rapid heart beat, tiredness, depression, thoughts of death, muscle soreness, tingling in his arms and legs, numbness, weird dreams (when he was actually able to sleep) and decreased appetite. He seriously thought that he was going crazy. It was not until I did some internet research that I finally linked all of his symptoms to this horrible drug. He stopped taking it on Friday of last week and each day since has been feeling better. He is not 100% back to normal yet, but each day seems to be better. It was a scary three day period while he was using this medication. Hopefully it will only take another day or two to get out of his system completely.

I have been on singulair for almost 2 years and i feel that it helps a lot actually when i don't have it my asthma acts up a lot, but it's only mild asthma so it's not too bad but it makes the difference. occasionally get a headache possibly attributed to it or more likely the zrytech however you spell that, but i like the singulair better than anything else and have had no thoughts of suicide or moodiness or anything weird.

My 7 year old son has been on and off singulair for a couple of years. He has been on it again for a month and we have noticed very aggressive behavior. He gets angry easily, nasty and into these rages where he actually is hitting me and slamming doors (even breaking the jam on his bedroom door!), just because he is not allowed to do something! After finding this site, I called the doctor(who of course did not call back yet) and took him off of the singulair. I am hoping the behavior gets better!

My 3 years old daughter was on Singulair for 8 months, that was prescribed by her Pedestrian from the Asthma clinic in Canada, Quebec. Lately, some of the symptoms of adverse effects are surfacing in her, including depression, action very emotional, constant having bad dreams (which causes tiredness), crying almost whole day in the daycare, refusing to eat and drink, refusing to join her favorite activities... Her Pedestrian told us there is no side effect on Singulair when she renewed the prescription 2 days ago. Because of my doubt about that, I started research on the web and found out that the early communication was issued by FDA. Of course, I took my daughter off from Singulair right away.

I work in the drug development clinical research field. I know that nothing the FDA or Health Canada will pursue until a lot of cases on adverse events (side effects) reported to them. Please everyone, if you or your child has had developed any side effects on this particular drug (Singulair), please report to FDA at once. It got me so upset is that this drug is constantly and widerly prescribed to children, and the Pedestrians are not caution enough to tell the parents. I definitely do not want to see other children suffer the same symptoms as my daughter had.

My daughter has been off Singulair for approx 2 months and is back to her old self. Talkative and happy! How about contacting the media to see if they would be interested in doing a story on the problems that have been associated with this drug. Yesterday morning there was a story regarding the poor health of our children-high cholesterol etc, and my first thought hmm-wonder if they are on Singulair. I think if more light was put to this drug, maybe we could get answers faster.

I have been feeling a sensation of pins and needles in my calves and a feeling of numbness in my feet. I know this is listed as a potential side effect but what are the indications? Also, dizziness and tiredness. I have been on Singulair for about 9 months.

Hi everyone, I just want to say thank you for all who shared on this site. I am a 47 year old woman. I have spent several hours reading posts last night and today, and discontinued my Singulair last night. I have been taking it for approximately 4-5 years for mild asthma. Since then my health has gotten worse and deteriorated rapidly in the past year. I have had chronic chest congestion leading to frequent infections. Have had pneumonia three times in the last three years and frequent bronchitis. In the last eight months I have been on antibiotics more often than not, along with Singulair and Advair and frequent rounds of prednisone. Still I continued to worsen. I have had a rash on both legs since March which clears up with a shot of prednisone, but comes back within a few weeks. I've been going to bed nights by 7:30 and still find it hard to get up and go to work. Energy levels would vary, but some days I literally felt as if I could not keep putting one foot in front of the other. I have always been the quiet, serious type and prone to depression, but this past year it has been getting progressively worse. I have become very antisocial and even missed my son's wedding because I was so stressed out about it. I have also had alarming hair loss and just feel that my body is in a very depleted state.
My doctor, an allergist, ran a number of tests, but could find nothing. He finally referred me to a specialist at a University. He did a bronchoscopy and tested for tuberculosis and sarcoidosis because I had very similar symptoms to both of those diseases. They were both negative, but they found a rare form of bacteria in my lungs that doesn't respond well to medication. They felt that it should run its course eventually. I'm sure all of the immune suppressing drugs I have been on have made it difficult to recover from this. Aside from a two week prescription for a form of sulfa which they felt the bacteria may respond to, I am off all other drugs. For congestion they have prescribed a therapy vest instead of medication. I am very anxious to see if being free of Singulair and Advair helps me to recover more quickly. Already on day one I feel a better outlook on life and even went on a shopping trip with my mother today :-) I can't say at this time what role Singulair has played in all of this, but am anticipating an improvement after reading all of your posts. Thank you.

I am nearly 60 yrs old and have been on Singulair for some time. I have noticed mood changes but something even more alarming. My blood pressure usually runs a bit low but since going on Singulair, it has gone up. I have also had many instances of feeling faint and having to sit down and lower my head. I've had two incidents of E.R. treatment due to irregular heart beat, feeling faint, and elevated B.P. When I quit taking the medication for several days, my B.P. was again on the low side and I never felt faint. Although an irregular heart beat is an identified side effect, elevated B.P. and fainting are not. I would like to know if anyone else has experienced these symptoms, as the doctors have told me these are not side effects of the medication.

In response to Wewe's post, I've been wondering the same thing. Since taking my daughter off Singular almost 2 months ago, I'm seeing a different almost typical kid. Four years ago about 2 months after starting Singular my daughter was diagnosed with anxiety. As her condition got worse she was diagnosed with depression. We started to see OCD and tics so they were added as a diagnosis It was determined that it was related to strep infections so she was diagnosed with PANDAS. She was started on Zoloft and klonidine. The Zoloft made her worse. Her fears of hurting herself got so intrusive she was hospitalized. Her cholesterol was high too. The Zoloft was discontinued and Prozac was started. She's had therapy all 4 years. She also neede physical therapy due to muscle and joint pain. Now she's doing better, off Singular. Does she really have PANDAS, OCD? I don't know. She's still on Prozac, we just did a slight decrease this week. Is this medication the trigger for underlying conditions. Learned behaviors can be unlearned, but are there lasting physical effects? If a gene has been turned on, can it be turned off? I wish we knew the answers to help all of our kids.

After reading all the horror stories on here, me and my husband soon began to realize that we were having a lot of the side effects listed here and not listed on my son's actual Singulair prescription. The side effects my son had were behavioral changes, irrational behavior, inattentiveness, not able to stay on task or stay still -- in fact he broke his arm twice being so hyper, yelling, screaming and just plain mean.

We took our son off of Singulair as a trial for a few days. Immediately we began to notice differences in his behavior. He wasn't as agitated and quick to yell or get angry. (He's only 5 years old). He actually would be listening when we would speak to him. He would sit calmy and read books and the one huge thing he would do was look at us and smile. He even said to my husband once, "I love you Daddy," which just brought tears to our eyes. I never realized what a Singulair fog he was in and what it did to him. Here we were pretty close to getting him evaluated for ADHD or even Aspergers. So now we're in the same boat as others that are searching for other asthma meds to give my son. Right now we have gone back to Pulmicort, Xopenex, Nasonex and Allegra. I'm so glad I read this forum because I was desperately searching for answers for my sons behavioral issues. Oh, by the way he was on Singulair for 1-1/2 years.

I have been on Singulair for about 6 weeks, the first 3 weeks I had a headache all the time, but that finally past. Now my joints hurt all the time, could this be form the singulair

I have been on Singulair for about 6 weeks, the first 3 weeks I had a bad headache and they told me that it would past, and it did. I know that my breathing is better, the only thing now is that my joins hurt all the time
Can this be from Singulair

I'm seeing some posts from parents who say their children have returned to normal after discontinuing the use of this medication. However, there seem to be a lot of diagnosed "ADHD" or "BIPOLAR" conditions. Are your children really returned to normal? Or have they been diagnosed with a psychological issue and are receiving treatment? There seems to be a connection here, even after discontinued use, especially male adolescents. Any thoughts?? The increase in cases of ADD, ADHD, AUTISM, etc has been multiplying at a very disturbing rate in the last 10 years. I'm thinking definite connection to the "new" breed of "receptor blockers". What is it triggering? Any thoughts out there? Lets post anyone with similar cases and see how many are out there.

I have only been taking singulair for about a month. I have noticed that I have become more irritable, grouchy, hateful and just numb, not really wanting to be around anyone, not caring about anyone else's feelings much. I also noticed I have become extremely lethargic, to the point of falling asleep at work as well as heart palpitations and stomach pains. I just started new birth control pills so at first assumed they were causing these side effects, that is until I looked up the side effects of this drug! I have over half of the side effects so I stopped it immediately and can already tell a difference in my mood. I have to sons age 11 and 14, both who have asthma and allergies. The took this medication for a few years with no side effects but have not taken it for about a year now. My youngest son however, has been diagnosed with ADHA and ODD and possibly BiPolar disorder. As I read the other posts, I realize the description of how their children act while on this drug is exactly how my son acts. I wonder if there can be irreversible permanent damage from taking this medicine? He has been on a number of ADHD drugs, none have helped except to make him stop eating and lose weight and he is small for his age, so I have taken him off everything. Has anyone else out there experienced what could be permanent damage from this drug in their children? Even after being off the drug for a year or so? If it could make me miserable within a month, what can it do when one takes it for years? Its sometimes hard to tell the effects of medicine on small children. My son prob starting taking it around 4 yrs old and took it til he was about 8 or 9. Just wondering if anyone else out there has had this happen to them or their children.

Update....since I posted in April, my son has not had any night terrors!! I am not kidding, I never imagined it was Singulair causing them...he sleeps through the night and seldom wakes up! He has been off Singulair for a little over 2 months and is back to the loving little boy we once new years ago! Please pass this on to anyone you know who has children taking Singulair...give these little kids their lives back!

~Melissa

Concerned citizen!!!
Just had to share the news! 3 months after stopping singulair and taking omega 3 (for last 3 months) has resulted in my 6yrs olds cholesterol going down from 236 to 202! Absolutely no diet change, in fact he has been eating worse due to throat condition/tonsils. Makes me go HMMMMM!!!

In 2003 at the age of 31. I had been taking singulair for over 2yrs. I started experiencing muscle weakness and I got to the point I could not sit or lay down. I was extremely in a lot of pain and taking large amounts of pain medicine. It went on for several weeks. I went to the doctor because I was having muscle spams or what I thought was a ruptured disk. I had a MRI done and it didn't show anything. I was sent to a back surgeon and he checked me out and wanted me to list all my medications. I began to tell him about zyrtec and singulair. He asked me how long I had been on singulair? I told him almost 2 years. He told me to get off of it right now because it would kill me. He said the singulair was deteorating my muscles
and causing me to have muscle spasm. I had no muscle tone. He sent me to a massage therapist 3days a week for 6 weeks and I came off of the meds. The doctor told me he had at least 10 patients that had happen to them.That was a wake up call. The doctor also told me his wife was on it 6 months and started throwing up blood and took her to the ER. All because of singulair and my kids have been on it for 3 years and have not had one problem. They are 10 and 7.
My husband is a pharmacist and he had not heard anything bad about it. He filled out a card about the side effect. It only happens in 2% of people taking it.

with your doctor. KEEP ALL DOCTOR AND LABORATORY APPOINTMENTS while you are using this medicine. Laboratory and/or medical tests should be performed periodically to monitor your progress or check for side effects. Check with your doctor for more

I just pulled this of the aarp site about 5mg singulair,did any ones doctor do lab work,not mine. When i called Merck this week to report side effects the rep asked if my son had ,follow up blood work,

I have been on SINGULAIR for 2 months now, I am a very active person, I do lot of sports. First thing I noticed was severe tiredness that affected me during practicing. Sleep disturbance and insomnia became very common, I had to shift from ZYRTEC to BENADRYL to be able to sleep.
Last week I did a blood test, the scary thing was elevated ALT levels ( almost 3 times the normal level ). I excluded all factors that could cause that. Nothing but Singulair. I have stopped it and I will go for a course of sylimarin and retake the test in 1 month.

My son began taking singulair when he was 6. About that time we were hading into the school years. He was labeled as a "special" child from that time on. Impulsive, aggressive, angry, anti-social, etc. He had a hard time focusing at school and every day was a battle. About 5th grade, after 3 schools, he was diagnosed with ADHD. I never, ever thought that it could be this medication. He was on it for about 4 years off and on during allergy season. I transferred him to a private school for children with behavioral issues and as time went on through therapy and special schooling it seemed to get better. I look back now and see that our "good" times were when he finally went off it for good. The beginning of his Freshman year was great! He had a 3.58 GPA, making friends and finally happy. The unfortunate thing is now that puberty has really kicked in, we are back to the old behaviors but much worse. Impulsive, angry, anxious, afraid of the dark, afraid of death. Violent thoughts, impulsive and very unhappy. I can see now that my son never had ADHD. He was misdiagnosed because thier were no warnings at that time. I don't think it ever "goes away". Even after years of being off of it. Something with the puberty hormones is re-triggering this behavior. IT IS LONG TERM!!!!! Even after discontinued use. Please, please keep an eye on your children. I AM SO ANGRY FOR HIM!! Also, for me. Special school $400 month, psychologist appointments, $300 month, my poor Son in a dark place I can't get him out, PRICELESS. . .I want my Son just to be happy. Thank you all for sharing your stories, it gives me strength that I need for him.

My 10 year old son has taken Singulair on and off since he was 5 years old and has been on it for the past 3.5 years. My son at an early age was affected by a bad marriage and then the divorce when he was 5 yrs old. So we always suspected that his behavior issues were caused by this and I had done everything I possibly could to give them the help he needed to get over and through his issues. He was held back his first year of Kindergarden and during his second year midstream he was placed in a special class for behavioral problem children. Nothing ever seemed to help him, everytime we would see some progress and encouragement we were always blind sighted by a behavior that was always worse. Two steps forward and them 5 steps backwards. I always knew that his problems would never get better overnight so I just kept on going. He was diagnosed with ADHD but because he has some ticking issues I had to put him on Strattera which was did not do a thing for him. I always described him as my Dr. Jeckyll/ Mr. Hyde child. He could be really good and sit still and behave but I think he had to try really hard to do so. He eventually was always overpower by the impulse to show negative behaviors. Defiant, extremely impulsive, always negative and completely miserable all the time. He also went through phases of compulsions. There was always a compulsion of the month- germs, bathroom habits, noises, repetitive words. He hated school and always complained of a stomach ache which i thought he was always faking to get out of school. He had confrontations in school everyday for most of the day. I often thought some of this was because of being tired all the time. We had battled over bedtime every single night. He was terrified to go to bed alone, I tried everything to get him to sleep alone. I wore myself out falling asleep next to him, I would then go to my own bed only to be up with him half the night going back and forth. I gave in many a night and slept with him just so we could get a good nights sleep. At age 8.5 I finally got him to go to sleep alone but the lights haf to be on and he has to know that I am still awake before he will fall asleep. He would always say he didn't want to go to sleep because when he does he has bad thoughts about me and people that he loves. He always had an extremely hard time excepting the word "no"- he would flip out and hit his head with whatever was handy, throw things, break things, scream holler etc. It would take hours to get over it. When he did he would be very remorseful and lovable. He was always in turmoil. Finally in February of this year, this graduated to a new level where he would want to just kill himself and would actually go and pull a knife out of the drawer and just shake with anger as he held the knife to his throat. I was terrified although i really didn't think he was going to harm himself he just wanted to scare me. Then at the end of March when i first heard the news about the possible side effects of Singulair, I had only heard about the suicide effect. Oh great just what I needed was this medicine causing him to do that. The doctor was thinking about taking him off if this summer because he wanted to see if he out grew his seasonal allergies so I took him off immediately. Well I had no idea about the other side effects until my son turned into a completely different kid. School noticed a huge difference in him! His grades went up, his is able to control his behavior, he is happy he is NORMAL. I never suspected this drug as the culprit due to the timing of taking it. Our lives have changed completely. When i first found this site, it seemed as though some of the parents were writing about my child. It is amazing. My son still has some old habits to break but overall he is a wonderful and normal 10 year old boy. He did not outgrow his seasonal allergies but Allegra seems to help in through it. I get so angry- his whole early childhood was ruined by this medicine. He is a labled kid in our school system. This whole experience has opened up my eyes. Thank you for letting me share my story.

Update. The count down is on. Next week on Tues my 6yr old son will be having his tonsils removed. Only 5 months after the adenoids were removed. I am hoping once this is over the improvements I have seen will just get better! His sinus drained in April, 9 days after coming off Singulair after battling sinus infections for entire year or more actually. When his sinus drained the infection went right into the tonsils and he has had tonsillitis ever since. One thing I wanted to share is that around the same time he came off singulair we started omega 3 supplement. Both my son and I stopped Singulair the same day. We both started the Omega 3. Last week I had to stop his dose because of the upcoming surgery because it can thin the blood. I noticed this last week his nasal allergies kicked in. He did pretty good through this allergy season and wasn't on any meds a lot of the days. I hardly had to take allergy meds this time around also. Im allergic to trees/grass and this is usually my bad time. I really feel the omega 3 has helped a lot!!! I am also waiting to get the results of his blood tests to see if his cholesterol has gone down. Just wanted to share!

I'm 50, a lifelong asthmatic (since age of 4). I started taking singular in 1999, Time Magazine's cover story back then. In the spring on 2001 I had stopped taking it. I got sick and my doctor had me taking it again. I told him subseqently that I had noticed changes in my moods. He dismissed the notion. I worked on wall street. 911 came and I was put on antidepressants (zoloft 200mg/day and gabatril 8mg a day). I lost seven years of my life. Yesterday I spoke to my pharmacist. I'm now on disability (respiratory, depression and anxiety). Medicare Prescription plan would not pay for Advair. The pharmacist to my surprise pointed out that depression was written up as a potential side effect of singular. I have read that head meds may leave 70% of those taking them left them still depress and with sleep disorders etc. I have been off the head meds for 9 months now. The mental fog has cleared, (from not being sedated).). An my depression continues unabaited as it has for the past ten years.

I also found out that MAXAIR is back after being discontinued. I used it for at least ten years (in the 80 & 90's). It has nt steroids, long lasting compared to albuteral as an emergency inhalher and precluded the need for multiple asthma meds. My life changed when Maxair was not being bottled which was just about the time Singular came out. I doubt it will undo 10 years of environmental injury and damage caused by singular and steroids. I also believe the best advice for keeping me breathing freely was drinking lots of water, (distilled, I bought a machine rather than carry a gallon a day from the store.). was truely life improving. It allows your body to flush out the impurities our modern day life threatens us with. I read the posts on this site and was compelled to share my personal experience(s), for you to consider....

My son, now 10...has been on singular off and on, since I don't' know how long...today was the second time he was intentionally hurting his cat. He has told me time and time again about visions while he was awake, violent ones, he argues with anyone and everyone. He has no friends at school. Last year I took him off all his medications to see why his behavior was so drastic, he got so calm, it was like a new boy, but then when he started back to public school...he had to be put back on them again, and again with the singular...
If it was not for this site..I would think my son was sick mentally. But after this...he will see his doctor tomorrow and no more singular...
When I took him off all the meds I told his doctor I was really worried about his behavior and they said it will be okay...he went right back to just out of control. Could not sleep, concentrate at school or at home. He is so smart and he is failing school..not because he is slow, but they kept saying he was add...but when I home schooled him and took him off his meds...he was so great, obdient..not perfect by no means, but just a normal boy...
I hear him right now, in the other room, fighting imaginary people...he seems to go go go..and with no sleep...the dreams in the day time I just thought were his imagination...but now that i hear about other children like him...they are to him real..just like he tells me..he also always tells me how mad he stays..he says all the time I am just angry mom, and I would say at what..he just says everything...
Thank God for this site....now i know..it is not in his head, it is just like I told his doctor...it is his medication..now I know just the one it is..
THank you all..
God Bless all the others here suffering with the same problems...it is just shocking that we as parents and patients, even after telling the doctors, are right...I feel vindicated...I will be printing this off and taking it with us to the doctors...

Hi everyone
My little boy who is nearly two was put on Singulair as a preventative.
I did check on forums when we started using Singulair and I was concerned that there has been descriptions of negative affects. Always trying to be objective I rationalised that the people in this forum are a small part of the greater Singulair population and as a result there was a low risk of negative affects on my little boy.
I have to say I think I was wrong. As soon as he was using Singulair, he had restless nights of sleep. Every night he would cry off and on until 2am and I guess he was so tired he slept. During the day he was very short tempered and became upset very easily. We put this down to tiredness. After 10 days of the lack of sleep for parents and little one, we told our doctor.
He advised to take him off Singulair for 5 days and make observations and then put him back on. Last night, his first night off Singulair was bliss. Not a sound. He had a great sleep. As I type he is now having another great sleep.
Let us see what happens after 3 more days and after putting him back on Singulair.
It would seem that if we are correct and that Singulair is a cause of an issue for my child, am I a quasi beta testing laboratory for a drug?
We are from Australia.
Thank you for reading.

There are studies like the one below that show a link between suicide and dysregulation in the brain. So we need to learn the relationship between the cysLT1 and cysLT2 receptors in the brain and those in the study.

The Journal of Neuroscience, February 11, 2004, 24(6):1478-1485; doi:10.1523/JNEUROSCI.4734-03.2004
Neurobiology of Disease
Dysregulation in the Suicide Brain: mRNA Expression of Corticotropin-Releasing Hormone Receptors and GABAA Receptor Subunits in Frontal Cortical Brain Region

Zul Merali,1,2 Lisheng Du,1 Pavel Hrdina,1 Miklos Palkovits,3 Gabor Faludi,4 Michael O. Poulter,5 and Hymie Anisman1,5

1University of Ottawa Institute of Mental Health Research, and 2Departments of Psychology, Psychiatry, and Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada, 3Laboratory for Neuromorphology, Hungarian Academy of Sciences and Semmelweis University, 1094 Budapest, Hungary, 4Semmelweis University Hospital, 1125 Budapest, Hungary, and 5Institute of Neuroscience, Carleton University, Ottawa, Ontario, K1S 5B6 Canada

Corticotropin-releasing hormone (CRH) and GABA have been implicated in depression, and there is reason to believe that GABA may influence CRH functioning. The levels of CRH, and mRNA for CRH-binding protein, CRH1, and CRH2 receptors, as well as various GABAA receptor subunits (1, 2, 3, 4, 5, , and 2), were determined in several frontal cortical brain regions of depressed suicide victims and nondepressed individuals who had not died by suicide. Relative to the comparison group, CRH levels were elevated in frontopolar and dorsomedial prefrontal cortex, but not in the ventrolateral prefrontal cortex of suicide victims. Conversely, using quantitative PCR analyses, it was observed that, in frontopolar cortex, mRNA for CRH1, but not CRH2, receptors were reduced in suicide brains, possibly secondary to the high levels of CRH activity. In addition, mRNA of the 1, 3, 4, and receptor subunits was reduced in the frontopolar region of suicide victims. Interestingly, a partial analysis of the GABAA receptor functional genome revealed high cross-correlations between subunit expression in cortical regions of nondepressed individuals, suggesting a high degree of coordinated gene regulation. However, in suicide brains, this regulation was perturbed, independent of overall subunit abundance. These findings raise the possibility that the CRH and GABAA receptor subunit changes, or the disturbed coordination between these GABAA receptor subunits, contribute to depression and/or suicidally or are secondary to the illness/distress associated with it.

I just started using Singulair a few days ago. I am 54 years old and just started coughing at night only. I would be fine during the day and then never failed, at night I started to cough keeping me awake. I was given antibiotics, narcotic cough syrups but it only helped temporarily and then I went back to coughing nights only again. So as I mentioned, I started taking Singulair a few days ago because my physician thinks I have developed allergies and Singulair is noted to help night coughs. It is helping my night coughs but I still cough a few times at night and now I cough quite a few times in the day when I never use to cough in the daytime. Wondering if Singulair is worth taking as the symptoms are becoming opposite? I hate taking drugs and don't know if I should find a safer alternative? Help, anyone? Thank you

I started full body internal itching after taking 10 days of Singulair. The physician that prescribed it said it couldn't cause itching. My new doctor tested for Lupus, I have an autoimmune disorder called Churg Strauss. After undergoing several steroid treatments and 3 days of IV Prednisone I got some relief. This has been going on for 6 months now. The itching becomes severe enough to make me want to commit suicide. Luckily it is pretty controlled by taking nightly doses of Atarax along with Periactin. Thank God I found a doctor who cared enough to search out the symptoms and help me get thru day by day.

Here is an example of the fact that the medical community recognizes that there are gene based drugs. Because Singulair is modeled to be a receptor antagonist to the cysLT1 receptor and the cysLT1 receptor is a gene, I'd say that Singulair should be described as a gene based drug. I don't really care how anybody wants to play with the definition. CysLT1 is a gene with known variations. Why isn't there just an "across the board" warning for all gene based drugs that unexpected side effects are possible???? And, that doctors should watch out for individual reactions.

WMJ. 2005 Aug;104(6):61-6.Links
Gene-based drug prescribing: clinical implications of the cytochrome P450 genes.Musana AK, Wilke RA.
Department of General Internal Medicine, Marshfield Clinic, WI, USA.

The Institute of Medicine recently mandated an increased effort to improve patient safety and reduce medical error. With the description of genetic polymorphisms in the drug metabolizing enzymes, the field of pharmacogenetics may improve medical care through a reduction in both therapeutic failure and adverse drug reaction. Investigators at the Marshfield Clinic in central Wisconsin are piloting the process of gene-based drug prescribing in a variety of contexts. This paper reviews the field of cytochrome P450 (CYP) genetics and explores factors that impact the utility of this information in clinical practice.

PMID: 16218319

I am finally writing after reading these posts since the end of April. That is when I took my 11 year old son off singulair, in an act of desperation. He has been on singulair on and off for about five years for seasonal allergies. He started again in mid-March so it could get into his system, before the allergies started. Immediately thereafter his behavior changed. He was arguing on a daily basis. He would hit, kick or trip me when he was angry. He was starting to destroy things in anger. He seemed to be fueled by anger. It was affecting the whole family. He was starting fights with his younger brother, my husband's heart was palpitating and I was crying every day. I heard about Singulair side effects and looked it up. I saw that it caused behavioral changes and out of desperation, took him off, not knowing what to expect. We had three days of total peace, then on the fourth day another outburst. Then my son told me he had taken a singulair the night before. That was it. I threw every pill in the garbage. He no longers acts like that. It's been almost two months so I am convinced it was the Singulair. By the way, he always complained of headaches, stomach aches and would scream in his sleep. Who knew - it was the singulair all along.

I just posted a link to a site and when I returned to the computer it was deleted .I will try again *****
Wonder how that keeps happen? I am not that great on the computer. My son tried to teach me some things but I am on my own now and maybe I am doing something wrong,
Kate

Hi,
I wanted to post this link just to give some small consolation to our concerns about the lack of awareness THAT DOCTORS HAVE ABOUT SINGULAIR.This is a voluntary online informational site,that doctor's can join. It provides updated information on serious label changes and safety concerns on drugs.Most doctors at this point still get snail mail updates,in the paper shuffle a lot of information gets misplaced.The AMA would like to have all information come in online,eventually.The link is ******
read it and tell me if you think more can be done By the way my pediatricians office does not have online communication.Our life is forever changed because of that ! Information is playing a vital role in this drugs destructive path ,or the lack there of information.Again this is voluntary for the Doctors to sign up .In this modern day of communication how does important information not get where it is the most useful, I ask you?When drugs are making multi billion dollar profits,that would be an educated guess.I am doing another interview with CBS affiliate out of Boston on the 23rd of June,they contacted me.I hope it will reach more people who are still unaware of this drugs serious potential side effects.If any of you parents have some connection to media ,please use it to your best advantage to get this very important information out to the publicAlso so many of you ask how to help.Contact your local Senators and keep bothering them to reach out to the FDA to expedite this investigation. Make a pain in the butt out of yourself and be persistent.I will try to make reference to this site so your stories are heard. Dave and I are coming up on a year since our son passed on to our lord .Still fighting Kate and Dave M.

My nine year old daughter has been on Singulair for just over a month because of seasonal allergies. Early this morning she woke up with a terrible nose bleed. She has never had a nose bleed in her life before today! Could this be because of the Singulair?

My son is 6 years old and he has been on and off Singulair for about 2 years. He was off since last Fall 2007, but was put back on in April 2008 for allergies. He began telling me that he was having "dreams" during the day. He would then tell me these totally bizarre thoughts, "dreams" that he was having. They were very strange and perverted and violent. I asked him why he was saying this stuff and he said, "I just can't help it, they pop into my mind." I thought that he was going through a phase because he was bored. He is in 1/2 day kindergarten and I attributed this to too much television and boredom. I was thinking that someone was feeding him this crazy information (kids on bus, class, etc.) and he was repeating it to me. He was too showing OCD symptoms, afraid if he touched his feet- "is that dirty??" afraid if he touched someone's hand, "is that dirty if I touched Tim's hand?" He would also cry and whine often over the simplest things. I thought this was a phase. Our prescription for Singulair ran out and I did not fill. I started noticing a change over a week's time period. My little boy who was coming to me several times a day with bizarre "dreams" had not mentioned them at all. His compulsive behavior has stopped and so has the whining. I feel lucky that I did not fill the prescription because I would not have even thought it was the singular, since there are no side effects like the one's I mentioned above on the label. I am sick about this!!

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.

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 was reading some research from the 90's where one researcher called montelukast an inverse agonist. So then, I looked for any thing more current on that subject. It would seem that genetic variation is again involved.

1: J Pharmacol Exp Ther. 2004 Apr;309(1):102-8. Epub 2004 Jan 12. Links
Inverse agonist activity of selected ligands of the cysteinyl-leukotriene receptor 1.Dupré DJ, Le Gouill C, Gingras D, Rola-Pleszczynski M, Stanková J.
Immunology Division, Department of Pediatrics, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Québec, J1H 5N4 Canada.

Cysteinyl leukotrienes (CysLTs) are associated with several inflammatory processes, including asthma. Due to this association, considerable effort has been invested in the development of antagonists to the CysLT receptors (CysLT(1)R). Many of these molecules have been shown to specifically interact with CysLT(1)R, but little is known about their impact on the conformation of the receptor and its activity. We were especially interested in possible inverse agonist activity of the antagonists. Using a constitutively active mutant (N106A) of the human CysLT(1)R and the wild-type (WT) receptor coexpressed with the G(alphaq) subunit of the trimeric G protein, we were able to address this issue with ligands commonly used in therapy. We demonstrated that some of these molecules are inverse agonists, whereas others act as partial agonists. In cells expressing the CysLT(1)R mutant N106A exposed to Montelukast, Zafirlukast, or 3- phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid (MK571), the basal inositol phosphate production was reduced by 53 +/- 6, 44 +/- 3, and 54 +/- 4%, respectively. On the other hand, 6(R)-(4-carboxyphenylthio)-5(S)-hydroxy-7(E),9(E),11(Z),14(Z)-eicosatetraenoic acid (BayU9773) and 1- -phenyl ethanone] (LY171883) acted as partial agonists and alpha-pentyl-3- benzyl alcohol (REV 5901) as a neutral antagonist. However, in cells expressing CysLT(1)R and G(alphaq), all antagonists used had inverse agonist activity. The decrease in basal inositol phosphate production by ligands with inverse agonist activity could be inhibited by a more neutral antagonist, confirming the specificity of the reaction. We demonstrate here that Montelukast, MK571, and Zafirlukast can act as inverse agonists on the human CysLT(1) receptor.

PMID: 14718577

Is heart racing one of the side effects? I have problems with edema which are worsened by Singulair and Zyrtec. Vivid Night terrors depression, anxiety are standard also made worse. Headaches extremely high blood pressure and nausea. I have been off the singulair for a month. I am Zyrtec Free as well.
I too will rely on my inhalers. This drug should not ever be prescribed for children.

Antimicrobial Agents and Chemotherapy, July 2004, p. 2624-2632, Vol. 48, No. 7
0066-4804/04/$08.00+0 DOI: 10.1128/AAC.48.7.2624-2632.2004

The Antimalarial Potential of 4-Quinolinecarbinolamines May Be Limited due to Neurotoxicity and Cross-Resistance in Mefloquine-Resistant Plasmodium falciparum Strains
Geoffrey S. Dow,1* Michael L. Koenig,2 Lesley Wolf,2 Lucia Gerena,1 Miriam Lopez-Sanchez,1 Thomas H. Hudson,1 and Apurba K. Bhattacharjee1
Divisions of Experimental Therapeutics,1 Neurosciences, Walter Reed Army Institute of Research, Silver Spring, Maryland 209102

Received 16 September 2003/ Returned for modification 25 November 2003/ Accepted 3 March 2004

The clinical potential of mefloquine has been compromised by reports of adverse neurological effects. A series of 4-quinolinecarbinolamines were compared in terms of neurotoxicity and antimalarial activity in an attempt to identify replacement drugs. Neurotoxicity (MTT assay) was assessed by exposure of cultured embryonic rat neurons to graded concentrations of the drugs for 20 min. The 50% inhibitory concentration (IC50) of mefloquine was 25 µM, while those of the analogs were 19 to 200 µM. The relative (to mefloquine) therapeutic indices of the analogs were determined after using the tritiated hypoxanthine assay for assessment of the antimalarial activity of the analogs against mefloquine-sensitive (W2) and -resistant (D6 and TM91C235) Plasmodium falciparum strains. Five analogs, WR157801, WR073892, WR007930, WR007333, and WR226253, were less neurotoxic than mefloquine and exhibited higher relative therapeutic indices (RTIs) against TM91C235 (2.9 to 12.2). Conventional quinoline antimalarials were generally less neurotoxic (IC50s of 400, 600, and 900 for amodiaquine, chloroquine, and quinine) or had higher RTIs (e.g., 30 for halofantrine against TM91C235). The neurotoxicity data for the 4-quinolinecarbinolamines were used to develop a three-dimensional (3D), function-based pharmacophore. The crucial molecular features correlated with neurotoxicity were a hydrogen bond acceptor (lipid) function, an aliphatic hydrophobic function, and a ring aromatic function specifically distributed in the 3D surface of the molecule. Mapping of the 3D structures of a series of structurally diverse quinolines to the pharmacophore allowed accurate qualitative predictions of neurotoxicity (or not) to be made. Extension of this in silico screening approach may aid in the identification of less-neurotoxic quinoline analogs.

My 9 year old son only took Singuliar for about 5 weeks. He had side effects almost immediately, he was so aggressive, angry all the time, headaches, stomach ache and feeling like he was going to throw up, bad nightmares, a horrible rash, biting his nails, not focusing in school and got into trouble all the time, no appetite but his little body seem puffy all over. He has been off this medication for 3 months and he is still not 100%. He cries at little things and still has the same rash and with meds it is not going away. He had to change schools as he still was having problems in school. He just seems like he is not the same little boy and something is just not right. I do not know what to do at this point. Doctors say it should be out of his system by now, but if it is than there is permanent damage to his brain as he is just not the sharp little guy he was. We have had to take him out of all sports. Anyone else having these same problems???

We have an other update. Day four being off Singulair. I have seen a big change, back to his normal self (thank God). Everyday that he is off, he gets better and better. Yesterday there wasn't even a rage fit. He is sleeping better and no more screams at the top of his lungs. The screaming was the first that stopped and every day the fits get less and less. I understand that a growing baby is going to throw a fit here and there but the fits he was having were not normal ones at all. The funny part here is that after I took him off of all meds except the astinel (sp?) he is better all around. No runny nose, no cough, no sneezing, NOTHING!!! Good luck with your little ones. All I can say is everyday that he is off this awful stuff he will return back to you a little at a time.

Who administers this site? I posted a side effect last night after I registered and then this morning I got an email saying there was a reply to my posting and when I tried to log in, my account was inactive and my posting had been removed, as had the reply to my posting. I don't know if it is because I put a link the an online reporting tool where the FDA is compiling feedback from people/or their children who have experienced terrible side-effects. Here is the link again and I urge you all to report your cases: http://www.fda.gov/cder/drug/early_comm/montelukast.htm

My son is 3.5 and has been on Singular for 2 months and just like all of the other stories about the other young children posted here, he is a different kid after being on Singular. Last night was the first night I took him off of it. All of the side-effects that are mentioned here are the same ones my son is experiencing, nightmares (screaming in the night), hyper, aggressive, reliving injuries from days past, the day care telling me that they now have concerns about how different he has been lately and the even used the term "bad behavior". They said he is hyper, he screams, not listening, aggressive. He is a favorite at day care since he is so loving, polite and kind. I know all parents say that, but pretty much anyone who has met him compliments me on how well behaved he is. I am even nervous to have people over since he seems out of control and I have found myself ensuring people that he isn't normally like this. I have taken him off as of last night and I am hoping he will get back to his old happy-go-lucky self soon. Does anyone know how long it can take to get this poison out of their system? I pray that there are no permanent side-effects.

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