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  • BDD Moderators: Keif’ Richards | negrogesic

Sodium Valproate (Epilim)

MatthewD

Bluelighter
Joined
Jun 13, 2009
Messages
229
Basically, what does this drug do exactly? My psychiatrist subscribed it to me today in addition to my regular Lexapro (15mg per day) and Valium (5m 4x per day). Apparently since the Valium wasn't fully curing my anxiety, he thinks this will stop me from getting frustrated/irritated (with bickering/arguing family), help me concentrate and calm down a bit.

Any experiences and thought? P.S. Don't feel afraid to get technical, I can't find anything detailed about how this drug works besides "it does this"...
 
From a quick wikipedia source, it looks like its an anti-seizure medication that can be an effective mood stabilizer. Strangely enough, there isn't very much information on its method of action, although I imagine it involves the GABA system..
 
I skimmed this article and it seems quite detailed on its use in seizures, bi-polar, and migraines.
After more than 40 years of clinical use, the mechanisms of action of valproate in epilepsy, bipolar disorder and migraine are still not fully understood. However, recent findings reviewed here shed new light on the cellular effects of valproate. Beyond the enhancement of γ-aminobutyric acid-mediated neurotransmission, valproate has been found to affect signalling systems like the Wnt/β-catenin and ERK pathways and to interfere with inositol and arachidonate metabolism. Nevertheless, the clinical relevance of these effects is not always clear. Valproate treatment also produces marked alterations in the expression of multiple genes, many of which are involved in transcription regulation, cell survival, ion homeostasis, cytoskeletal modifications and signal transduction. These alterations may well be relevant to the therapeutic effects of valproate, and result from its enhancement of activator protein-1 DNA binding and direct inhibition of histone deacetylases, and possibly additional, yet unknown, mechanism(s). Most likely, both immediate biochemical and longer-term genomic influences underlie the effects of valproate in all three indications.
http://www.springerlink.com/content/u689114448254644/

edit:
summary for those without access.
NSFW:
Overall interpretation
A plethora of diverse data has been published over the
past several years in an attempt to explain through a
variety of mechanisms the efficacy of valproate in its
different clinical indications. These data support the
involvement of valproate in several pathways in which
it had not been previously implicated. Yet, reviewing
this information, it is remarkable that the number of
cellular targets that have been proven to be directly
affected by valproate is very small, and this number
becomes even smaller when considering the relevance
of some of these direct targets to epilepsy, bipolar
disorder or migraine, at least as we understand their
pathophysiology today.

There is little doubt that valproate directly inter-
feres with GABA metabolism to increase GABA
brain levels, and that this effect likely plays a
significant role in the immediate control valproate
exerts over epileptic seizures [5] and possibly also
mediates some early therapeutic effects of val-
proate in bipolar disorder [8] and migraine [11] . The
direct inhibition of GSK-3 by valproate, however, is
at best controversial [70] , and the inhibition of
microsomal long-chain fatty acyl-CoA synthase [42]
still awaits further reproduction and substantiation
of its relevance to human disease. Likewise, what
underlies valproate inhibition of brain myo-inosi-
tol-1-phosphate synthase activity, and whether this
is at all relevant to bipolar disorder therapy, still
needs elucidation [44] .

In contrast to the latter cellular targets, valproate-
induced changes in the expression of multiple genes,
mediated at least partially through the direct inhib-
ition of HDAC [18, 121, 122, 142] , have been
repeatedly demonstrated and may very well be
relevant to the therapeutic effects of this drug through
interference with intracellular signalling, e.g. the
inactivation of GSK-3 [73] , and neurotrophic and
neuroprotective effects, e.g. through the promotion of
BDNF expression [27] . Considering the large number
of genes whose expression is altered by valproate [108,
109] , it is reasonable to hypothesise that gene
expression changes plays not an insignificant role in
the long term effects of the drug. Future research
should try and assess for every newly discovered
valproate-induced cellular effect whether it is depend-
ent or independent of HDAC inhibition or AP-1 DNA
binding promotion by this drug. Nonetheless, many
genomic effects of valproate cannot be explained with
our current knowledge of its influences on AP-1 DNA
binding and HDAC inhibition, and additional mech-
anisms through which valproate, or its metabolites,
can affect gene expression should be sought.

In conclusion, influence of valproate at the genomic
level may provide insights into therapeutic effects
relevant to all three indications of epilepsy, migraine
and bipolar mood disorder [12, 124, 138] . The ��unified
field theory�� for the mechanism of action of valproate
in neuropsychiatric disorders possibly comprises acute
effects mediated essentially through the enhancement
of GABAergic transmission followed by a variety of
longer-term effects primarily resulting from gene
expression changes.
 
From a quick wikipedia source, it looks like its an anti-seizure medication that can be an effective mood stabilizer. Strangely enough, there isn't very much information on its method of action, although I imagine it involves the GABA system..

Well, I am having the same experience. I even asked the head Psychiatrist what Sodium Valproate does, and although I pushed for specific in-dept neurological explanations, he basically said "it will stop you from having mood swings and getting irritable and in general calm you down.".... He assured me that although it was Bi-Polar and Anti-Epileptic medication, he has no doubt that I am NOT bi-polar. He just said that the medication does what he thinks I need, and that is to calm me down and help me focus. Essentially replacing my old Ritalin prescription with a non-stimulant, as I get stimulant-anxiety these days. And I need Benzo's to counteract the anxiety (but still get the positive effects from both).

Anyway... Looking forward for some veteran pharmacologists to blow my mind. I don't even know whether I want to take this stuff at the moment. The only thing I can find on it are well-documented side effects haha. But I have taken my first dose.
 
I skimmed this article and it seems quite detailed on its use in seizures, bi-polar, and migraines.


edit:
summary for those without access.
NSFW:

Holy shit, that's quite beyond the scope of my uneducated understanding of the brain. If someone could translate that a little? I'm really keen to learn.
 
I think the link amapola provided (and the text he pasted, thank you again amapola :)) is about as in-depth as its going to get. I recommend reading through that first.

There is little doubt that valproate directly inter-
feres with GABA metabolism to increase GABA
brain levels
, and that this effect likely plays a
significant role in the immediate control valproate
exerts over epileptic seizures [5] and possibly also
mediates some early therapeutic effects of val-
proate in bipolar disorder [8] and migraine [11] . The
direct inhibition of GSK-3 by valproate, however

That's probably the more important part. :)
 
I think the link amapola provided (and the text he pasted, thank you again amapola :)) is about as in-depth as its going to get. I recommend reading through that first.



That's probably the more important part. :)

So, basically it's an inhibitor of the breakdown of GABA inducing *insert intelligent word here* and would potentate drugs that promote GABA stimulation/inhibition. Meaning Valium should work better on this?
 
^In theory yes. It's exact method of action still isn't completely understood but it looks like the most likely way its working is by causing there to be more GABA levels...
 
So, it's basically the SSRI of GABA, instead of Serotonin.

So as Lexepro (or another SSRI) is to MDMA
Sodium Valproate is to a Benzo (or other GABA enhancing/breakdown-inhibiting) drug.

Am I right?
 
So, it's basically the SSRI of GABA, instead of Serotonin.

I wouldn't say that, I would just say the "method of action is still unknown". We know increased levels of GABA are the end result of whatever that method of action is.

Possibly, I wouldn't go so far as to make the comparision between GABA-related drugs and 5-HT (serotonin) related drugs, because those two neurotransmitters are quite different in their function in the first place.
 
Here is how it increases GABA levels.
As an acute biochemical effect, valproate has been
shown to increase brain levels of the inhibitory
neurotransmitter g-aminobutyric acid (GABA) prob-
ably by inhibiting succinic semialdehyde dehydrogen-
ase, consequently increasing brain levels of succinic
semialdehyde, a metabolite that inhibits GABA
transaminase thus preventing GABA catabolism [5] .
Evidence also suggests a direct inhibitory effect of
valproate on voltage-gated Na+ channels, suppressing
high-frequency firing of neurons, and possibly indirect
effects on non-GABAergic neurotransmission [5, 6] .
The big question about it's mode of action is on the other bipolar, epileptic, and migraine and how these might be treated in the long run. Reread the article's summary.
...valproate directly inter-
feres with GABA metabolism to increase GABA
brain levels, and that this effect likely plays a
significant role in the immediate control valproate
exerts over epileptic seizures [5] and possibly also
mediates some early therapeutic effects of val-
proate in bipolar disorder [8] and migraine [11] .
It then goes on to list other possible mechanisms of action which are unproven but could have important effects.
 
Last edited:
I wouldn't say that, I would just say the "method of action is still unknown". We know increased levels of GABA are the end result of whatever that method of action is.

Possibly, I wouldn't go so far as to make the comparision between GABA-related drugs and 5-HT (serotonin) related drugs, because those two neurotransmitters are quite different in their function in the first place.

I believe you, everything I read basically says "well we really don't know." Purely assumptions, based on theoretically-accurate assumptions. It's sort of scary really... Do I really want to be taking a drug that we know little to no about?
 
Here is how it increases GABA levels.

I can follow that context to some extent. But it honestly confuses me, there's a lot of unfamiliar terms and expressions in there. Can anyone give a 'crash course' on the terminology step by step. In simple terms, basically a 'for dummies' explanation. This is intriguing me, I want to be able to understand this stuff so badly.
 
I think it inhibits GABA-transaminase also, preventing breakdown of GABA.

As well as its known ion channel interactions at voltage-gated sodium channels.
 
So GABA-transaminase = the amino acids that break down GABA-acid? I know nothing of ion channels or what they are, what they do and what they are related to either. But hey, if someone can explain I'll do my best to comprehend. I wish I could have done this full-time at school... I probably wouldn't have failed.
 
Here's your crash course on voltage-gated ion channels. (Wiki does a much better job of explaining it than I do).

Here's the bigger article on ion channels in general. That will probably help to.

Article on GABA. Also important that you read that as well, GABA's function in the CNS is a special one. It's job is to regulate the activity (or excitability) of the neurons in the CNS.
 
Try this thread in ADD for some bedtime reading :)
Erowid/BlueLight Neuropharmacology Text

I can follow that context to some extent. But it honestly confuses me, there's a lot of unfamiliar terms and expressions in there. Can anyone give a 'crash course' on the terminology step by step. In simple terms, basically a 'for dummies' explanation. This is intriguing me, I want to be able to understand this stuff so badly.
It doesn't really matter. All it means is that Valproate is working on the GABA levels indirectly by inhibiting an enzyme, which increases the levels of a substrate, which inhibits another enzyme, which increase the levels of the substrate GABA... or something like that.
 
Try this thread in ADD for some bedtime reading :)
Erowid/BlueLight Neuropharmacology Text


It doesn't really matter. All it means is that Valproate is working on the GABA levels indirectly by inhibiting an enzyme, which increases the levels of a substrate, which inhibits another enzyme, which increase the levels of the substrate GABA... or something like that.

I'll note that I have taken in the advice of the previous poster before you and will read up on those Wikipedia pages and articles. Thank you for your productive responses.

Now, you basically did what I was asking for. Simplifying a complex formula for me into something understandable. Thank you very much. So I'm basically taking something that indirectly inhibits something in a chain reaction. I wonder what repercussions come from that? Haha...
 
I was thinking more long-term, unknown/lab-rat type discoveries. Lets pray. I know it comes down to the person most of all when it comes to drugs, but in my situation (from the information provided), does anyone have any input on whether or not this drug would actually add much of an anti-anxiety and anti-depressive effect (on top of the Valium and SSRI's)?
 
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