Parallels symptoms and conditions

Is there a potential explanation for the adverse psychiatric side effects of montelukast?

In my opinion, there are at least some very good clues based upon the work of the Chinese researchers.

A 2006 report indicated that they had localized (meaning found it was there) the CystLT1 receptor (same as the receptor that montelukast
Singulair blocks) in the neurons of the brain tissue of rats. In order to do that, they injected rat brain's with NMDA to cause a chemically induced state of excitotoxicity. Excitotoxicity is a common factor in Central Nervous System disease. They concluded that both 5-LOX and CystLT1 were upregulated by the excitotoxicity that they artificially created
with the NMDA. Therefore, there would be a potential link between neuron activity and CystLT1. Nerve cells are damaged by excitotoxicity. These researchers used NMDA to cause nerve damage which caused the CystLT1 to show up. NMDA was often used in human behavior studies to cause brain damage. They would then try to observe whether behavior was compromised to conclude what areas of the brain determined what behavioral response.

So I was thinking about the Chinese researchers as I was reading other posts. One post interested me particularly regarding the mother who described behavior that seemed like hypoglycemics when their snack doesn't arrive on time. So a light bulb went on. Glutamate, another excitotoxin, can build up in the brain to a level that is damaging if humans become excessively hypoglycemic. If glutamate concentration around the synaptic cleft reaches too high a level then neurons die. Clinically, it really does seem that many people experience things that sound like the effects of hypoglycemia. It could be only a coincidence. But then again, maybe not.

The Chinese researchers found the CystLT1 receptor in the rat brain neuron after brain damage. They found the CystLT1 receptor in the normal human brain in the microvascular endothelial cells and in neuron and glial-appearing cells in brain trauma or tumors.

What role does the CystLT1 play in brain function? If it exists in brain tissue, we can assume that it does have a function. If it plays a role in preventing or repairing neuron damage due to excitotoxins, then there would be a very direct link between Singulair and adverse psychiatric side effects.

http://www.chinaphar.com/1671-4083/27/1526.htm

The bottom line is that Merck owes people who take Singulair further research regarding it's effect on the brain.

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