NMDA channel blockers and seizure risk

[Frogster]

for some background info on NMDA channel Blockers such as Ketamine, PCP, Tramadol, ect see also http://www.bluelight.ru/vb/showpost.php?p=9582530&postcount=931

Since birth, i suffer from cerebral palsy with left sided spastic. I never experienced a generalised tonic-clonic seizure, but it happened sometimes that i experienced more or less bad drug induced myoclonic episodes especially affecting my spastic body-parts. Those were quite scary nonetheless, but clonazepam always cured it to my big relief.

The three worst myoclonic eisodes were:

1. After snorting 100 mg Bupropion i experienced some cocaine-like euphoria soon followed by a myoclonic attack. Very stupid from me, as Bupropion has a well known history of inducing seizures. But being a Norepinephrine and Dopamine Reuptake inhibitor, i have to guess that the seizure inducing pharmacology of Bupropion isn't understood yet. I highly suspect at least some NMDA action here.

2. While being on 150 mg DXM after a dose of approx. 100 mg MDMA. That was the second day in a row where i consumed MDMA so i was already drained of dopamine that day. Also strobelight and rhythmic music seemed to badly worsen the condition. I had to retreat from audiovisual stimulus immediately and administer clonazepam.

3. After taking only 100 mg Tramadol before bedtime. I suddenly awoke out of nothing in the worst myoclonic attack. Again Clonazepam to cure it. That experience made me hate Tramadol even more than Bupropion.

I would theorize the following:

a) NMDA channel block + serotonin release or reuptake inhibition: increased seizure risk

b) NMDA channel block + norepinephrine release or reuptake inhibition: increased seizure risk

c) NMDA channel block + inhibited dopamine release (also counts for dopamine depletion): increased seizure risk

d) NMDA channel block + dopamine release or reuptake inhibition: decreased seizure risk

c) could be the consequence of a) and b), so maybe one just has to consider c) and d).

I might be wrong, but it would explain why Bupropion, DXM and Tramadol lower the seizure threshold, while Ritalin, Ketamine or opiates other than Tram do not.

 

[sekio]

Monoamine release is correlated with seizures (esp. norepinephrie), I think there's a much simpler explanation then getting NMDA involved.

 

[(zonk)]

^i was just about to say that... Dont blame the NMDA, it's the stims u must stay away... Actually i yhink NMDA antagonists aregood at preventing seizure or atleast certain types

 

[Frogster]

ok, but NMDA agonism is for sure pro-cunvulsant. So would the inhibition of NMDA channel opening have an anti-convulsant effect, that's pretty clear to me.

I rather suspect some kind of rebound glutamate or glycine release after NMDA channel block that would increase seizure risk. I suspect that norepinephrine would reinforce that effect, whereas dopamine would rather attenuate it.

btw. i never had any roblem with stims alone. The mechanism of seizure induction is more compex than only having too much free norepinephrine in the synaptic cleft. And id would not explain the episode that i had with Tramadol.

 

[sekio]

Buproprion, Tramadol, DXM, and to a lesser extent MDMA (MDMA is more of a releaser) all act as norepinephrine reuptake inhibitors.

 

[ebola?]

2. While being on 150 mg DXM after a dose of approx. 100 mg MDMA. That was the second day in a row where i consumed MDMA so i was already drained of dopamine that day. Also strobelight and rhythmic music seemed to badly worsen the condition. I had to retreat from audiovisual stimulus immediately and administer clonazepam.

This combo (mdma and dxm) readily induces serotonin syndrome was, which IIRC, also includes siezure-like activity.

ebol

 

[(zonk)]

...btw. i never had any roblem with stims alone. The mechanism of seizure induction is more compex than only having too much free norepinephrine in the synaptic cleft. And id would not explain the episode that i had with Tramadol.

U really gotta look into the pharmacology of the substances u use before u make these assumptions.

1.Tramadol is a norepinepherine reuptake inhibitor(stimulant)hence the claim of it being "non-narcotic". NE can convert to dopamine and vice versa+i think tramadol may be serotogenic as are most opiates(could b wrong), but i knew someone with seizures and ANYTHING speedy even coffee would make her feel much more prone to experiencing an episode, which is why she was hooked on downers
2.Bupropion is pretty much a stim "alone" except for some activity at nicotonic receptors.
3,It seems like every episode happened on a stimulant but this doesn't mean everytime u take 'any' stimulant that u will get a seizure everytime