Levetiracetam (Keppra) — Another Possible Potassium Channel Modulator?

would keppra work for reactive tinnitus if you have slight hearing loss ie,6htz 30dbs

 

Xexus Danny...you are still saying this???!!! Where did you get this piece of info???

Ref. Keppra and basics, including zero evidence that it works on Kv3 channels see this post in other Keppra thread:
https://www.tinnitustalk.com/thread...d-for-my-hyperacusis.8946/page-23#post-146596
And from that:

Note: For the non 'research oriented' but interested in Keppra, you may want to just skip down to the "key take-aways" in part 2. of this post...as yes, I do tend to drone on. Not changing my 'spots' now, sorry.

@svintegrity ...Ta much for add on info. post as indeed backs up the stuff I seem to be finding as dig deeper. Also much thanks to @111 down under, for two excellent tomes on Keppra (and Brivaracetam) which for the die-hards will get the 'links' below.

1. ~ OK...so for all you could ever want to know about Keppra (& Briv.) here is a link from a more than exhaustive study out of Germany in 2012. And don't get put off by it being in German to start with as the main text is in English. However,do be put off with the fact that it is 170 pages long before the 'references' start!!!

http://hss.ulb.uni-bonn.de/2012/3068/3068.pdf

I did not review it all. No way! However I did skim, and also looked for (search/find) key things of interest to me re. my whole initial approach to taking Keppra...that it was a Kv3.1 drug, like Autifony's famous star - or at least that Keppra had strong elements of Kv3.1 possible modulation.

Short answer...There is absolutely zero back-up or mention of that in this German paper. There is small reference to generalized Potassium channels within epileptic MOA ideas...and yes, in relation to our old comrade in arms (or hell, perhaps to some), Retigabine.

Conclusion on all that, to me OK, is that Keppra is not a Kv drug of any significance.

Thus I am no longer thinking of it in those terms, and no longer acting on it in those terms. Results, are as prior stated...I'm dropping off and not heading for 'break the doors down' dose effective inter-extra cellular neuronal saturation levels. *[And yes, Keppra is considered 'dose linear' but I consider that more relevant for the epilepsy modelnot the 'model' I had in mind. Also the Australian TGA paper next makes me wonder a bit WTF is going on with "dose" anyhow...or my concentration perhaps!].

2. ~ OK...the second paper, c/o the Australian TGA (which does some good work indeed...as per our research efforts on Retigabine, etc., etc.). This one is shorter and more readable, with some easier 'take-aways' that could be of interest to some here considering Keppra, or already taking it. *[And yes, I need to re-read it again (and maybe again!) to see what the hell is going on re the different "studies" quoted. That there is hardly any difference between doses of 1,ooo mg total v. 3,000 mg total, and that maybe Europeans act in a hugely different manner to Americans at even lower dose differentials???!!! Ummmmmmmm...must be me! Though the issue could just be that these 'problems' are all within the "Add-on AED Therapy" department, where more than just one AED...than just Keppra, is involved!. Plus they do not indicate which prior AEDs were actually used...So this could all be a red herring for us anyhow].

http://www.medicines.org.au/files/txplevet.pdf

Key take-aways, summarized in short (thus incomplete) sound bytes:

- Due to its complete and linear absorption, plasma levels can be predicted from the oral dose of levetiracetam expressed as mg/kg bodyweight. Therefore, there is no need for plasma level monitoring of levetiracetam.
Translate as: Body weight and size matter! (Also noted c/o @svintegrity).

- Following single dose administration (20 mg/kg) to epileptic children (6 to 12 years of age), the half-life of levetiracetam was 6.0 +/- 1.1 hours. The apparent body clearance was approximately 30% higher than in epileptic adults.
Translate as: Yeah you younger folks with less 'wear and tear' on your body parts are likely to unload Keppra faster and better than us more 'matured' (screwed over by various sundry health insults) folks.

- Monotherapy (i.e. = just Keppra, no other AED add-ons)...The recommended starting dose is 250 mg twice daily which should be increased to an initial therapeutic dose of 500 mg twice daily after two weeks. The dose can be further increased by 250 mg twice daily very two weeks depending upon the clinical response. The maximum dose is 1,500 mg twice daily.
Translate as: The Aussies seem to believe in classic titration - both in and out of Keppra use. Mmmmmmm...

- Overdosage: The highest known dose of levetiracetam received in the clinical development program was 6,000 mg/day. Other than drowsiness, there were no adverse events in the few known cases of overdose in clinical trials.
Translate as: Go wild! Compared to Trobalt, "Twinkies" may be more harmful to your health than this stuff. Well, as usual, not everyone is created equally and treat accordingly.

Ummmm... OK think that's about it for my Keppra 101. Now just observation and reflection...Wunderbar! Or possibly..."Shit, that is a bit of egg in the face!" could be more appropriate, depending on your disposition.

Best, Zimichael

 

"The SV2A, a presynaptic vesicle protein, was thought to be
involved in synaptic vesicle exocytosis and neurotransmitter
release (45). Several studies have demonstrated that the synaptic
vesicle protein 2A
(SV2A), a presynaptic vesicle protein, is the
binding site of LEV
in the brain, with which this drug can interact
to modulate the function of SV2A
(1, 6, 46, 47).
W
ith the aid of
the LAIGN program, we further evaluated the similarity of amino-
acid sequence between the SV2A
protein and the
α
-subunit of
K
v
3.1. Notably
, the portion in K
V
3.1
α
-subunit (human:
NP_001
106212), to which the sequence of SV2A
(human:
AAH00776) shares the similarity (36.2% identity), was found to
be located extracellularly at 385-431.
This region was located in
the S6 segment of the K
V
3.1 channel.
This comparison leads us to
speculate that the LEV
molecule binds to similar docking
region(s) to block
I
K(DR)
as well as to interact with SV2A
protein.
In fact, cortical neurons
in vivo
are subject to varying overall
levels of stochastic synaptic background activity
, which is
particularly intense during active states of the brain (48).
The noise itself is shown to generate an effective potential function
for the dynamics that is asymmetric and bistable. In our
simulations, LEV-induced changes in membrane potential tend
to be responsive to extraneous factors that control the resting
potential, such as synaptic input or neuromodulation.
Furthermore, based on our simulation results, the adding effect
of inhibition of
I
K(DR)
under the condition in which inhibition of
I
Na
occurs, causes the termination of AP firing, reflecting the
practical add-on role of LEV in Na
+
channel blocking therapy,
such as phenytoin or carbamazepine (49).
Voltage-gated potassium channels have become potentially
important molecular targets in modifying action potentials in
various disorders including neuropsychiatry disorders,
cardiology and oncology (50, 51). In addition to Kv3.1, there are
still several components contributing to
I
K(DR)
, including Kv 1
and 2 subunits. Although ubiquitous, in different tissues, the
components of the potassium channels and their physiological
function vary (52). Adequate modulation of these potassium
channels including
I
K(DR)
and
I
K(erg)
would potentially be useful in
clinical treatment (50, 53).
Taken together, from our study, the effect of LEV on
I
K(DR)
(Kv3.1), could provide a therapeutic potential in treating
epilepsy"


https://www.researchgate.net/public...ntribution_to_the_firing_of_action_potentials

 

@Danny Boy ... This study you reference is that "Huang study" again, which if I recall, we have been over before. I am not going to wade through it all again. But my memory serves, it was the only one with speculative reference to KV3.1 influence as part of a huge laundry list of neurotransmitters/synaptic trigger bio-chemicals/channel modulators and so forth, that had possible potential neurological implications for the MOA of Levetiracetam. There were just too many darn things that LEV triggered to say anything for sure!!! And the more recent studies post 2009 seemed to refute any reference to Kv3.1, etc., etc.
Yes it may have Kv3.1 action...but so do probably three dozen other AED's (anti-epileptic drugs) out there that have the classic "Mechanism of Action not understood" as their by-line!

Thus the words "may be" are more suitable than "is" or "does"...in my layman's scientific, but very thoroughly covered research on Keppra, and talking to some Kv researchers about it's MOA.

Zimichael

 

@Zimichael : my line of thinking is that if you swallow the various pills out there which may have impact on the various Kv-channels - all at once (and just once) - then I am pretty sure the person's tinnitus would go away...

 

@attheedgeofscience ...and if you don't want to try your novel approach there are always "the darts"!
Pin up names of all the common AED's out there (let alone the 'speculative ones')...or print this handy list below (which leaves out a lot of others I have run into, for some reason). Stick it on a wall, then just throw a dart and see which name it hits. Try it, and it may darn well affect your H, and/or your T!!!

NOTE: The observant will note that the list below does not even include the most common group of AED's that indeed a lot of us use! Our well tried and true (yet addictive) Benzodiazepines!!! That bunch could add another half dozen to the list below. *[Thus you could print out this list that does include them as major line, common AED's] ... http://www.healthline.com/health/epilepsy/medications-list#Broad-SpectrumAEDs3

• Carbogen modified release
• Convulex
• Desitrend
• Diacomit
• Diamox SR
• Emeside
• Epanutin
• Epilim
• Epilim Chrono
• Epilim Chronosphere
• Episenta (prolonged release)
• Epival
• Frisium
• Fycompa
• Gabitril
• Inovelon
• Keppra
• Lamictal
• Lyrica
• Neurontin
• Nootropil
• Phenytoin Sodium Flynn
• Rivotril
• Sabril
• Tapclob
• Tegretol
• Tegretol Prolonged Release
• Topamax
• Trileptal
• Trobalt
• Vimpat
• Zarontin
• Zebinix
• Zonegran

 

I can say I'm genuinely curious to see what would happen if someone were to do that - although any other result that death would surprise me.

This is why you shouldn't let me run clinical trials.

 

I have been trying this drug (Keppra in France) for several months by varying the dosage between 250 mg and 3000 mg per day. No effect on my tinnitus, no side effects.

 

Has anyone tried Biviracetam which is similar to keppra but suppose to be very effective for epilepsy?

 

→ Effect of Antiepileptic Drug Levetiracetam on Cochlear Function

"Audiogenic seizures."

Maybe why some with reactive tinnitus get relief. I think 4-5 benefitted here.

Levetiracetam is also mentioned here for hyperacusis caused by irritable neural pathways:

(Source)

Levetiracetam could be worth a look!

 

Are you going to discuss this further with a provider? Being that reactivity is my debilitation factor, something like this is like dangling a possible amazing carrot in front of me, however I worry about side effects and the coming off of it eventually and what possible hell that could be. It would be even more helpful to know a general timeline for Dr. Shore's device. If its not available in the USA 4-6 months from now, that would further make me consider something like this more. It's crazy to read @Viking's post and a few others who basically reported reactivity/hyperacusis just vanished.