• BASIC DRUG
    DISCUSSION
    Welcome to Bluelight!
    Posting Rules Bluelight Rules
    Benzo Chart Opioids Chart
    Drug Terms Need Help??
    Drugs 101 Brain & Addiction
    Tired of your habit? Struggling to cope?
    Want to regain control or get sober?
    Visit our Recovery Support Forums
  • BDD Moderators: Keif’ Richards | negrogesic

Sodium Valproate (Epilim)

If your doctor thinks it might be beneficial he is much more qualified to make that decision that we are. It might merely be one of many option he is considering if it doesn't work as well and the only way of finding out is by giving it a shot.
 
If your doctor thinks it might be beneficial he is much more qualified to make that decision that we are. It might merely be one of many option he is considering if it doesn't work as well and the only way of finding out is by giving it a shot.

To be honest, for some reason I trust a collaboration of the more intelligent/knowledgeable/qualified people here than single qualified (to what standard?) doctors or even Psychiatrists.
 
When it comes to treatment the method of action is not nearly as important as the results. There are many medications where we don't know how they work, just that they do work. So we use them. Your doctor will know what this drug is indicated for and statistics on how it has helped others in the past. It is true they can sometimes be wrong, but in a case like this I doubt there is someone who is going to be able to say it would be better to not take it, and doubt even more that you should listen to them.
 
When it comes to treatment the method of action is not nearly as important as the results. There are many medications where we don't know how they work, just that they do work. So we use them. Your doctor will know what this drug is indicated for and statistics on how it has helped others in the past. It is true they can sometimes be wrong, but in a case like this I doubt there is someone who is going to be able to say it would be better to not take it, and doubt even more that you should listen to them.

Seconded. We're not doctors, I am a patient of psychiatry myself (I have really bad anxiety disorder), and I feel that, they, on a whole, do a great job. They do need to test things to see if they're working, the best thing to do is give the Epilim a shot, and if it doesn't work, talk to your doctor. Chances are he'll switch to something else until he finds something that works best for you. In all probability, the Epilim will work. The last thing you should do is go against his advice after taking just one dose...
 
Ion channels come in two main flavours, voltage-gated and ligand-gated, although voltage-gated ion channels can have binding sites for modulatory compounds, many nasty plant toxins, and an awful lot of the toxins produced by invertebrates, and cnidarians affect voltage gated ion channels.

Examples of such include the famous tetrodotoxin, puffer fish poison, of fugu fame, that imfamous sushi produced from very, very carefully prepared blowfish, which blocks TTX-sensitive sodium channels (and also found in the venom of the blue-ringed octopus, the california newt, a certain species of marine flatworm, and toads of the genus Atelopus)

TTX blocks those sodium channels, preventing an action potential (the current passed though nerves when the ion channels open and the cell fires in response to stimulation), causing paralysis, saxitoxin, or paralytic shellfish poison acts in the same way, although at a different binding site, whereas veratrine and related alkaloid toxins from Hellebore species, along with the venoms of the deadly, and very bad-tempered brazillian wandering spider, along with delta-atraxotoxin and the versutoxins of the funnel webs spiders in of the genus Atrax and Hadronyche lock sodium channels open, causing spontaneous, repetitive firing of nerves, resulting in a massive adrenergic storm, causing muscle cramps, sweating, severe tachycardia and severe increase in blood pressure, along with possible pulmonary oedema. Most scorpion toxins act by fucking with voltage-gated sodium or potassium channels (with the exception of the species Hemiscorpius lepturus, which is exclusively cytotoxic, and rather than neurological symptoms, causes horrendous flesh-eating effects, like that caused by recluse spider bites)

There are two main superfamilies of receptor expressed on cell surfaces (I am ignoring nuclear receptors located within cells here), metabotropic receptors such as GABAb do not form an ion channel, and instead of directly inducing ion currents within cells, signal more slowly than ionotropic receptors, and mediate their effects by inducing the release of second-messenger chemicals within the target cell, such as enzymes, transcription factors etc.

Ionotropic receptors on the other hand, such as GABAa, and the NMDA, AMPA and kainate type glutamate receptors signal far faster, and like other receptors are composed of complex protein subunits, arranged in such a manner as to form a central pore. this is the ion channel, and activation of the receptor by binding of an agonist drug/the natural neurotransmitter to those protein subunits, which can be complex enough to have multiple different binding sites, always one for the endogenous neurotransmitter, but often one or more allosteric modulatory sites causes a change in the 3d conformation of the receptor protein/ion channel complex which allows the channel to open for a time, and pass an ion flux.

The ionotropic receptors are those which express a ligand-gated channel, and induce the firing of an action potential by the binding of an agonist, voltage-gated ion channels do not depend on binding of a neurotransmitter or drug, but instead, the chance of firing an action potential depends on the voltage potential the cell is at, after a certain threshold is reached through sufficient depolarization of the cell, the voltage-gated ion channel opens, and passes current.

An allosteric binding site is a recognition site seperate from that for the main neurotransmitter, and can bind either positive (stimulatory in nature of the receptor expressing it) or negative (doing the reverse, inhibiting neurotransmission) and is dependent upon binding of a ligand at the orthosteric site, the main binding site for neurotransmitter.

GABAa is a good representative receptor of the ligand-gated ion channel flavour, it is made up of 5 seperate subunits, which form a central pore, and which passes chloride ions. Different subunit pentameric combinations result in receptors selective for different allosteric ligands, of which there are many types, and which expresses a large variety of allosteric sites, including that which binds benzos, another for barbs, one binding loreclezole and one of the active compounds from the sedative herb valerian, one for neurosteroids such as pregnanolone, and negative modulator recognition sites also.

These are seperate from the binding site that binds the endogenous neurotransmitter GABA, the main CNS inhibitory neurotransmitter (damping down other signalling processes and neurotransmitter release), an allosteric modulator of any kind will not cause any action in and of itself, if applied to a cell in the absence of the orthosteric ligand no effect will ensue, benzos work by potentiating the action of bound GABA, increasing the frequency of channel opening, whereas barbiturates more directly gate the chloride channel, and hold it open for longer, allowing longer duration of the resultant ion flux, and are thus more dangerous, as the body has far less ability to compensate for overactivity at the receptor.

Applied on their own though, in an environment free of GABA, benzos, barbs etc will do sod all in the way of causing current flow, not unless GABA is also bound to the main site, or another agonist.

An example of a couple of representative orthosteric agonists at GABAa (there are not nearly as many direct agonists of this type as there are positive allosteric modulators, the structural requirements for an orthosteric GABAa agonist are much more demanding) include muscimol, the active psychedelic-ish, dissociative-ish drug from the fly agaric mushroom, Amanita muscaria, isoguvacine, and isonipecotic acid.

Sometimes an ionotropic receptor can have some characteristics of both ligand, and voltage-gated activity, the NMDA-type glutamate receptor targeted by the dissociative anaesthetics such as PCP, ket and memantine is such a beastie. Activation of the NMDAr requires binding of either glutamate or aspartate, the endogenous neurotransmitters, and the main excitatory neurotransmitter expressed in the brain (along with a co-agonist, glycine, at an allosteric binding site, and there is also another allosteric site recognising polyamines), once the agonists bind, activation of the receptor causes a magnesium ion, which at the resting electrical potential of the cell expressing the NMDAr sits in the ion channel, blocking current flow to be spat out, in a voltage-dependent manner allowing the now open channel to pass current.

There are a great many seperate kinds of ion channel of the voltage-gated flavour, the main superfamilies being channels for sodium, calcium and potassium, and within those families, there are a crapload of subtypes, with varying sensitivities to different ion channel toxins, for example, I will use the calcium channel.

A non-exclusive list, includes N-type calcium channels, which are expressed in neurons, along with P and R types also found within the brain. L-type channels which are involved in mediating muscle contraction, such as that of the heart (medicinally important drugs acting here are calcium channel blockers, heart medications which act to slow the heart rate down by inhibiting opening of L-type Ca++ channels), T-type and a couple of others.

Some of these are sensitive to say, tetrodotoxin, saxitoxin etc, whilst being insensitive to other drugs/toxins, for instance the neuronal N-type channel is powerfully blocked by omega-conotoxin derived from the venom of the venomous marine cone snails, whilst the L-type channels are highly resistant to blockade from omega-conotoxin, but are blocked by the heart drug nifedipine, whilst nifedipine doesn't block the neuronal type recognising ω-conotoxin.

Does that clear things up some? Valproate blocking Na+ channels (sodium channel activation is excitatory in nature, I don't know if this is exclusively the case, but it is certainly vastly the predominant nature) will decrease neuronal excitability, and result in the requirement of a greater stimulation of the nerve before an action potential can be fired, thus having an overall stabilizing effect on neurotransmission, and acting to prevent or decrease the propagation of the uncontrolled shitstorm of random nervous firing that is characteristic of an epileptic seizure.

Incidentally, valproate was discovered by accident, it used to be thought inert and be used in neurochemistry experiments on animals (uggh!) merely as a delivery solvent for drugs being tested, it was only discovered when eventually it was used to deliver a convulsant poison to an animal, and it was found to have lesser effect than expected, exposing it as an antiseizure drug.

Don't know if you are female or male, but do not take during pregnancy, it is well known to be teratogenic, and cause lots of nasty mutations (bad thing) and increase the frequency of autism (good thing)
 
I can't really say much, but wow. I need to sit down sometime and thoroughly read that through to understand it. But excellent post, you seem to know your stuff. I'm a Male by the way. I'll report back when I've had the time to probably understand your text! :)
 
According to a book I have laying around (The Color Atlas of Pharmacology, 2000, Lullman), the anticonvulsant* action of Valproate is attributed to noncompetitive (allosteric) binding to NMDA receptors, preventing influx of Ca+2 ions.


*This may be of some relevance, as anticonvulsants work to limit runaway brain activity in motor centers of the brain. Excessive neuronal excitation in inclined persons can cause a feedback loop of electrical activity, leading to a seizure. It is quite possible that this same mechanism is at work in areas of the brain that control emotional responses. Inhibition of signaling in these areas, however, may prevent impulses that would otherwise put your brain into the excited states that cause the irritability you've mentioned.



On a second note, I'm glad you're expressing interest in this area. As you can see from previous posters who probably are far more knowledgable than myself, there is a tremendous amount of information out there to digest. Most exciting of all, though, is how much is left to learn. For all we as humans know, many of the more complex processes of neurological function are still a mystery. Though such building blocks as ion channels and neuron structure are known, much is still left to be discovered about the way these networks interact to render human consciousness
 
Thats one of the things we know almost nothing about, how electrical activity and structural architecture of the brain translate to actual consciousness.

All very well to say 'NMDA antagonism=dissociative effects', and even to explain the mechanisms whereby the psychological effects such as odd significance getting attributed or imbued upon an inaniate object (as happens with schizophrenia also, which is also thought to be related to dysfunction of NMDARs), the NMDAr is a co-incidence detector, in essence, to pick up when event A triggers event B, etc, activated by input from excitatory AMPA type glutamatergic receptors, critical for synaptic plasticity, where synapses adapt to changing demands and environment, strengthening highly active, much used connections, and allowing for those of lesser importance to atrophy. I have a feeling that it might well manifest in a sense that way on a conscious scale also, antagonism of NMDARs resulting in the well known wierd arse sensations of objects or people having significance or connections between them relating to the person experiencing lessened NMDAr function, weather the schizo or the guy in a K-hole, or those with OCD, 'if I turn the lights on and off repeatedly X number of times, bad things won't happen'

But do we know how the reduction in NMDAr-mediated Ca++ and Na+? (IIRC NMDAr channels primarily pass Na+ with smaller quantities of Ca++)....no. We have so little knowledge in that area, that we probably don't even know what knowledge we lack.
 
Well they put me on sodium valproate (first 300, then 600 and finally 900mg) but first, it is more an anti manic than an anti depressive, at least the textbooks say that. So if you are unipolar depressive, look out for if you get increasingly depressed.

I had strange reactions to it, at first I liked it even when I don't have problems with mania unless I do too much drugs. It had pronounced anxiolysis and maybe you don't even need to combine with benzodiazepines - but, if it's primarily for anxiety, really in my opinion the first one to try were pregabalin or gabapentin. If you have a chance to get it, which unfortunately means to import from France (EU), tiagabine - Gabitril - is a nice drug. It's too an antiepileptic but this one works by inhibiting the reuptake of GABA analog to eg SSRIs. In low-ish doses it is an effective anxiolytic w/o much tolerance.
Last but not least we have etifoxine, which again is an anxiolytic similar in strength to lorazepam but lacks tolerance problematic and sedation.

Valproate is a strong medicine which affects many things and has potentially serious side effects like alopezia / hairs falling out (got this, and read it depletes biotin do you should supplement - still no notice from the manufacturer at all), hormone suppression or weakening the skeleton by activating a certain emzyme (see eg. wikipedia). I don't have the data to give even just a rough guess about the probability of those.

Just that the first like 4 months I was fine and then, either with time or from upping to 900mg/d, it became too much. Dry skin, falling hair, and began to feel weak and sick. Then I stopped (titrated down to not get rebound seizures, don't remember a particularl withdrawal yet probably increased tension and anxiety.

@apsig @Limpet_Chicken very interessant that it binds to NMDARs. It had some weird interactions with dissociatives that were hard to grasp but certainly potentiation both partially of the dissociation, and of some side effects. I wouldn't recommend this combination.

Smoking was never more fun and euphoric than while on sodium valproate.

To be honest, for some reason I trust a collaboration of the more intelligent/knowledgeable/qualified people here than single qualified (to what standard?) doctors or even Psychiatrists.
@MatthewD Yeah I am the same.🙃
 
Last edited:
Top