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NO and epilepsy

Ian Reynolds ijr at prophet.pharm.pitt.edu
Wed Nov 16 17:06:10 EST 1994

In article <3a80dr$eol at knot.queensu.ca> brad at chem.queensu.ca (Brad Jacobs) writes:

>        In my current research I have an interest in the role of nitric
>oxide in epilepsy.  Being a chemist there is admittedly a certain amount
>of the biochemistry which I do not fully grasp, and thus I wish to hear
>the opinion of others on the subject.
>        My survey of the literature on NO and epilepsy shows that at
>this time there is still much disagreement about the role of NO in
>the epileptogenic mechanism.  While some papers suggest that NO is an
>endogenous anticonvulsant, others suggest that NO inhibitors act in
>an anticonvulsant manner.

Welcome to the world of nitric oxide research.....where there is disagreement 
about almost everyting!

>        Given this mix of experimental evidence is there any therapeutic
>advantage to a targetting of NO action in the CNS?

NO synthesis or action would ostensibly seem to be a good target for therapy 
of a number of things in the brain, including acute neurodegeneration, memory 
acquisition and perhaps epilepsy.  The difficulty comes, both in interpreting 
the literature and in this approach, in actually hitting the target.  NO seems 
to be pretty important in controlling cerebral blood flow in addition to doing 
lots of interesting things to neurons, and altering cerebral blood flow does a 
bunch of things to brain function that could be misinterpreted as an action 
directly in neurons.

Thus, to be able to get at epilepsy one needs to get at the neurons rather 
than the vasculature.  Drugs with this specificity mostly exist as rumors 
coming from drug companies :>)  The specificity issue is complicated by the 
existence of the "endothelial" form of nitric oxide synthase in some neurons, 
along with the more common neuronal form.

It might be possible to do something with NO in epilpsy, but the complications 
involved make the pharmacology of the NMDA receptor look like the script to an 
episode of "Barney" by comparison :>)  

(Sorry to everyone who has not been introduced to the large purple dinosaur 

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