Levetiracetam (Keppra) — Another Possible Potassium Channel Modulator?

Hey @Viking

any progress with the Keppra? Have you increased your dose?

 

Is early. Today is 8th day at 1000mg in 2 dose. I don't wante create false hope. Other 6 days i will go on 750 + 750 and after the final step 1000 + 1000. At this time i have "only" a big improvement in hiperacusys (unaspected) and i don't know if it is related to drug.
I must be only patient and continue on this way.
Thank you for your support

 

Thanks for the update, Ivan

 

How bad was your hyperacusis before?

In my mind, T should be lower too if you do have indeed positive results with H...
Carry on!

 

unfortunately my hyperacusis was severe. a simple beep could turn my T from 25db to 100db + headache + nausea + + inability to perform daily activities. Currently I have only floating bilateral tinnitus. I rode the motorbike for 3 days with no consequences. I was in traffic Christmas without problems. I talked this thing to my neurologist, he says he does not know if Keppra can be useful for H. We're trying it in order to low my aberrant T.
I do not know how to interpret this event. Surely it had never happened before.
I will update you

 

you will stay on 1000 am monitor creatinine? (3000max)

 

At a dose of 1000mg is not necessary to monitor liver function or other. This is valid until 3000. It seems to be the antiepileptic less "harmful" currently on the market. I asked the neurologist if I had to do some analysis and he said not.
Hoping...

 

http://www.drugs.com/dosage/keppra-xr.html

here is states depending on kidneys problem that patiens from 500mg-100o mg, so they test ans day what is max dosage.

 

Dear @Zimichael,

The next documents refers to antiepileptic drugs. The following theory considers the hypothesis that the mechanism associated with tinnitus is similar to seizures.

1) From:
The mechanism of action of retigabine (ezogabine), a first-in-class K+ channel opener for the treatment of epilepsy *Martin J. Gunthorpe, y Charles H. Large, and z Raman Sankar

p 3/13: http://onlinelibrary.wiley.com/doi/10.1111/j.1528-1167.2011.03365.x/pdf



LEVETIRACETAM appears to act on reducing SV2A protein action wich attenuates the signal at the neurons input while Retigabine acts on potassium channels, when they are open, they increase the inhibition of neurons.
This looks like a nightclub. The boss chooses to prevent the most excited subjects to enter (SV2A) or he chooses to neutralize them once they came (KCNQ or Kv) to maintain normal activity in the disco! The first solution seems more manageable! Levitiracetam could works on tinnitus.

2) From:
EXPERIMENTAL AND SIMULATION STUDIES ON THE MECHANISMS
OF LEVETIRACETAM-MEDIATED INHIBITION OF DELAYED-RECTIFIER POTASSIUM
CURRENT (KV3.1): CONTRIBUTION TO THE FIRING OF ACTION POTENTIALS
* C.W. HUANG, J.J. TSAI, , C.C. HUANG, , S.N. WU

p1/11: http://www.jpp.krakow.pl/journal/archive/12_09/pdf/37_12_09_article.pdf

" Therefore, the inhibitory effects on slowly inactivating IK(DR) (KV3.1-encoded current)
may constitute one of the underlying mechanisms through which LEV affect neuronal activity in vivo."

It seems that LEVETIRACETAM reduces the KV3.1 channel. It seems to be the opposite of AUT00063 ( KV3.1 channel opener?).

LEVETIRACETAM seems to be two opposite ways in terms of influence on the activity of neurons. SV2A protein could have the major effect on tinnitus.

To treat Tinnitus, I think we want to INHIBIT abnormal activity of neurons: ACTIVATION of some Kv (or KCNQ) channels to INHIBIT neurons activity could be one answer among many others ...

Am I good?

I wish you all Merry Christmas

 

it is referred to KEPPRA XR (extended release) for patients (i suppose) who have the risk of forgot to take the second or third dose. in any case, I heartily thank you for the tip. If I have problems (I hope not) I will keep it definitely in mind.

 

WOW MEN!!!

we urgently need a neuroscientist. I'm confused by the two arguments (and related mechanisms of action) "increased At inhibition" - "decreased At excitation". I understand that the goal is the same. Restrict epilepsy. is intriguing to know how. Trobalt is definitely effective in the treatment of tinnitus (my opinion based on experience). Now I have your same dilemma. Levetiracetam can act "directly"?
Who knows how long it takes to find out. is my first week with Keppra (500 + 500) and I do not know if it is a matter of dosage or time ... tinnitus is fluctuating and less responsive to sounds. Loud sounds. Hyperacusis absent. Now. If I raise the volume of the stereo and then suddenly make down the tinnitus same far for a few of seconds. Then returns but do not overdo it.
Previously, when i raise the volume of the stereo, I raised the volume of the tinnitus.
I do not know what to say.
Many many many thanks for your research

 

I am agree with you!!!

@benryu What do you think of these previous thread?

Levetiracetam (Keppra) — Another Possible Potassium Channel Modulator?

I am so happy for you @Viking . My tinnitus behaved exactly as you describe before starting the Trobalt. With @Zimichael, I discovered that this is defined as: reactive tinnitus.

I hope you will be better and better with LEV.

 

Hey NGC891... Yeah, your're good! I think?!

The Keppra game is one of the harder ones in town! Indeed it seem that the LEV/Keppra works on the "delayed-rectifier" Potassium current/channels and that this is indeed a different mechanism to the Kv7 Retigabine approach. Truth is, I have never seen a decent answer to what Kv3, whether it be Kv3.1 or 2 does on this micro-neurological level. There is so little on Kv3 versus Kv7 published.

However I agree wholeheartedly with @Viking that we need a neuroscientist on board! Keppra mechanism of action is way above my pay grade. Though indeed it may work for tinnitus and in a safer manner and different manner than Retigabine.
However, I do agree that my "Ketamine and Tinnitus argument" holds water, and that is if Ketamine has been used so extensively as a general anesthetic why haven't more people come forward afterwards and said: "Wow it cured my tinnitus. What happened while I was unconscious in surgery?!" Though @benryu's statistics on why that is unlikely are sobering!!! I know this is about Trobalt below, but similar principles could apply to Keppra...

https://www.tinnitustalk.com/threads...-—-general-discussion.5074/page-13#post-57795

Now let's just talk about the chances of having a patient with all the conditions below:
Epilepsy: 50M out of 7B (http://www.who.int/mediacentre/factsheets/fs999/en/)
0,7%

Using trobalt/potiga: 25% of the market and I am being super generous here (http://www.fiercebiotech.com/press-...ease-800-million-2016-primarily-due-uptake-pr), they forcasted to do 200M a year.

Tinnitus: 10% of the world population (http://www.theguardian.com/lifeandstyle/2008/apr/17/health-and-wellbeing-health)

Access to high level medicine: 30% of countries representing 4,5% of the world population,http://apps.who.int/medicinedocs/en/d/Js6160e/9.html#Js6160e.9

In touch with the company medical: they had roughly 3000 patients for the trial (including phase 1): 0.000042%

0.7% * 25% * 10% * 4,5% * 0.000042% = 0,0000000033075% chance
this assumes everyone is willing to give a fuck for other people, understand what's happening, etc..

Chance of winning the lottery: 0.000007151% chance

So you are 2162 times more likely to win the lottery than having one guy able to report the positive impact of the drug to a relevant person.

So....MORE KEPPRA TRIALEES ANYONE???

Actually to be more accurate, this is what I call "SRT" = Sound Reactive Tinnitus.

Best, Zimichael

 

It's a major gain mechanism to increase the accuracy of neuronal responsiveness. By balancing the excitation drive with inhibiting inputs it increases the range of excitation that the neuron can work with.

Think of it like the brakes and the accelerator of a car. You can slow down by easing off the accelerator but the brakes provide an inhibitory input to slow you down quicker and vice versa. Using both brakes and accelerator you can control the speed of a vehicle far more accurately.

If you decrease the inhibition (the brakes) then the car speeds out of control (an epileptic fit) unless you also decrease the excitation (the accelerator)

The mechanism here is like getting some huge ceramic brakes for your car and fitting a speed limiter too. Potassium is your brake cable and sodium your throttle cable.

Hope that makes sense.

 

Thank you for your "mechanical explanation". I really appreciate it.
However today is most strange and bad... i wake up with lower T more marked on left side 6000hz pure tone. After 4 hours the T go all on the right side... ever 6000hz but more loud.... now are 10:40 pm and i have took the second dose of 500mg 3 hours ago and i have a new spike all on the left side but changed in frequency 7500hz louder. Today there was a lot of movement in the head. Tomorrow i will go on 500+500+500 total 1500mg. I feel disheartened. I do not know if these spyke and these changes are a good or bad thing. The hyperacusis fortunately is absent, then at least I can watch a movie, but tinnitus is very strong. Who knows ... it was lower for 5 days... . Another 20 days, and I will give my final opinion.
Thanks all

 

@Viking ... Hang in there my friend, as long as things do not get too bad of course. As it seems to be evident now that these KV drugs may have to "fight the brain/plasticity fighting back" so to speak. Like changing old habits perhaps. It is not easy.
Of course I don't know for sure, but I would imagine that the "brain patterns" of my same tone of T after 58 years (an E-flat Eeeeeeeeeeeeeeeeeeeeeeeee) must be incredibly entrenched. So changing that would be very hard. If it were to change I suspect it would be a "mobile" process, like has happened with @rtwombly.
When I took retigabine I got absolutely zero change in tone, or 'location feeling' of my T...just the increased H. So I think that maybe it is good that anything is changing in your T as it shows the drug is affecting the stuck/messed up neuronal signals that are causing the tinnitus.
How it will end up, I have no idea, but to me, if I would have had a "change" it would have given me hope.

However, I know how easy it is to talk from the side-lines, but unless things get bad for you and volume goes up a lot or H increases a lot, I would assume there may be a "fight" to find a new homeostasis.

Also, though...personally I would NOT expose myself to any degree of louder sounds, even to test how much you can tolerate. It feels unwise and risky to me. I would wait until the action of the drug is clear and then take it slowly into "sound". Motorcycles and so on....Ahhhhhhhhhhhhhhh???

My two cents. Good luck and hope things calm down for you.

Zimichael

 

@Silvine ... I follow your explanation in principle but I still don't see how it is working with the Keppra assumption re method of action.
I can see how the spike interval would be reduced by more modulation of the two factors = excitation and inhibition. But with overall steady-state tinnitus, I can't get whether the Kv3.1 gates are being activated opened, via excitation c/o the drug...or closed/slowed down via inhibition.

Maybe the mechanism with Kv3's may just be the opposite end of the chain to Retigabine Kv7's???

Any more thoughts on that???

Ta much, Zimichael

 

haven't had time to digest this thread, just wanted to say that i recall reading on a few epilepsy forums, at least on two occassions, that some people were taking retigabine as an add-on drug with keppra.

 

Thought as much! I'll try both.

 

@Danny Boy why you wanna try it if RTG is working for you at this point?

 

Lucky this morning, after a really bad day and night i wake up after only 3 hours of sleep with 5db T instead yesterday 80db. Today i will see my neurologist and shows to him the papers that ypu have found about keppra and try to take more explanations about his mechanism of action. Thanks @Zimichael . Thanks to all soldiers!

 

Good news Ivan, nice to hear it. Perhaps yesterday was just a bad day. Is your T generally better, or just better than yesterday and simply came to the state it was?

 

Generally my T is bad since i wake up at morning and go worse during the day. In this days i'm experiencing (over the big improvement in H) a constant fluctuation. For example...now i'm up by 3 hours and took keppra... waked up with lower t on left side...now is gone to the right side. Lucky same tone lower. Without meds the T was more marked on left side with apyke on right side. Now are 3 days of continuos changing in lateralization and tonality. Today will be the first day of 1500mg divided in 3 doses. Also i will see the neurologist. On the telephone conversation he sayd that transient worsening is normal in his clinical experience and he advice me to wait and resist. Also i have cutted clonazepam from 2.5mg to 1mg. Probably there is a miscellaneous of consequences in the brain.
After today "meeting" i will update you.
Many thanks for your support
I'm only tryng a way for the relief of sufference

 

Fluctuating may be a good thing. Hope you nail that bastard!

 

Little update after the visit "face to face" with my neurologist: he is eextremely honest, not take money, not gave false hope. The worsening of tinnitus yesterday...or (when we are considering the tinnitus as a brain seizure) in the first weeks of treatments are normal. He say that in epilepsy treatment, based on fMRI or EEG.often, the doctors takes months to find the right balance to get the drug to control seizures. They must use more than a single drug dividev in different time of day. Then i will continue. There aren't certainties or warranty. For @Danny Boy ...yes... administration both anti seizure is a realty in clinical treatment of refractary epilepsy but the doctor Rao sayd: "tell to your friend that he also taking an hard drug for epilepsy without haven't seizure. We gave, in the hospital for 15 days, the combination of existing anticonvulsants, most retigabine under close clinical monitoring. I do not want to scare but he should not do it alone. There are aspects of the EEG alterations of which he can not realize and could create discomfort in everyday life. In the hospital, after confirming the positive and negative response of the patient, we give the "green light" to the home treatment. So, dear @Danny Boy ....from the bottom of my heart ..... DO NOT MIX! If a drug is working for you off-label, there is no reason to add another without any certainty. The only certainty we have is that you can have serious side effects and unpleasant in your situation prevents...
Also about our discussion, he has invited me to not stop medication on 20 January,but to insist and resist for 2 or 3 month because in seizure is the same situation, unless you have serious side effects / persistant worsening. Even then, the drug should not be suspended immediately but always gradually. About the very important works showed by @Zimichael and @NGC891 the discussion is the same. Retigabine has an exclusive/innovative method for the seizure control and it is the most recent anticonvulsant under investgation and last chance in treatment of epilepsy without organic cause (where could be give an help the surgery...removing a lesion or implanting a DBS stimulator). Keppra is confirmed as an exclusive anticolvusant with 10 year of clinical experience in the treatment of seizure. unluky , as for other drugs, not ever work for all type of seizure.....because we are clear...here we are tryng to treat tinnitus as a brain seizure. Then there are adjusting, changing,adding....etc. It surely have a function in order to calming neuron firing. Hoping to be of some help, but above all that God gives us a hand.
Thanks all
Best wishes

 

@Danny Boy ...I would have to strongly agree here!

Hell's bells, it's obvious we have two 'novel' drugs that from my perspective (and that of some of those working with them), are not fully understood. When you add two unknowns together I think you are taking undue risk. Even just Trobalt is a considerable risk IMHO!

@Viking ...thanks so much for sharing that info from your Neurologist. As stated before, the MOA for Keppra: The precise mechanism(s) by which levetiracetam exerts its antiepileptic effect is unknown. ...matches the "unknowns" for Retigabine.
Though what is becoming clear is that they are really working differently on the Kv channels interface...despite both being Kv modulators that we know seem to have a "Tinnitus effect".

Thus we have two quite different drugs!

So bottom line, is we cannot compare Keppra to Trobalt in any 'direct line' fashion. Keppra may be a lot safer, and also a lot more available from less "skittish" docs! Now it may not be quite as heavy a hitter as Trobalt, but that may be a good thing!

So for people who have been following the Kv discussion, were considering Trobalt but have been afraid of it, perhaps Keppra is a really good alternative to consider!!!

*I am not a doctor, so this is not medical advice...you have to make up your own minds about the potential efficacy v. risks trade offs.

Plus I'm sure Viking would like some company!

Best, Zimichael

 

I myself would try it, perhaps I will, but I am currently under Gabapentin (Neurontin) for 1 month. No results yet, will discuss it with my doc if I will go on with it. Other options are:
1) Tegretol (mvc signs in my MRI)
2) Keppra
3) Trobalt

 

My dear friend;

i think for opinion/experience (about NVC) that you could be a pioneer in this specific clinical type of tinnitus.
The reasons: you have a clear diagnosys of neurovascular conflict.
Now all we know that surgery argumentation are not clear and successfully, then you "must" try all drug available before think to surgery.
Actually you are on Gabapentin, that i have taken in the past before and after surgery as an attempt to stop tinnitus, with baseline dose 300x3 to a max of 2400mg. NO RESULTS. Only side effects. On the leaflet of this controversal and under investigation for false indication on leaflet drug (Mechanism of Gabapentin is unknow) there aren't reasons to continue on this way. Pfizer who made the first tipe of Gabapentin called Neurontin must pay for false hope. http://www.bloomberg.com/news/2014-06-02/pfizer-agrees-to-325-million-settlment-over-neurontin.html
i know a person who has deteriorated his condition with Gabapentin prescribed for tinnitus: http://tinnitushomepage.com/neurontin/
When I think that Pfizer is funding Autifony are overjoyed. They have to make up for the legal fees and can not do more pictures of shit (at least this is my little hope)
The other side of coin is a combo that i have tried but i not advice, cause addiction: 0.50mg clonazepam + 300mg Gabapentin in single dose at morning can give relief in some cases...but between Gabapentin and Clonazepam i don't know who is the best bad choice.

1)Tegretol: drug of first choice in the treatment of trigeminal nevralgia. Facial nerve (VII) is very close to auditory nerve (VIII) where you have the possible responsible of conflict. Tegretol can work without high dosage. If it work you realize it in 1 week at only 200mg. Single pill. There is a similar drug with less side effect named Tolep (Oxcarbazepine) but at the same time of minor side effects, it has minor benefit effects on nevralgia. In any case Tegretol/Tolep you must check your liver function ever 30 days.
Little discussion: how Tegretol act in Tinnitus due to NVC. Think to 2 electric cable. One is the bloodvessel and another is auditory nerve. The conductive material of the electric current is copper, covered with plastic. If for many years this 2 cable rub ever, due to the continuous heartbeat, the myelin covering the auditory nerve will corrode (plastic cover) went in contact with the offending bloodvessel, generating the "spark" which will result in an aberrant signal from the periphery to the center (CNS), better known as TINNITUS...probably...
Now you pioneer could be discover to be able to suppress this abnormal activity (spark) due to anatomical problem with Trobalt,acting on the CNS and ignoring the periphery (there aren't certainly).
Other way, tegretol who act on the CNS but releasing (it is subastantially a calcium/sodium antaghonist) low current in CNS in order to deviate/ignore the aberrant signal due to NVC.

Keppra is too one unknown, probably i'm the only one person who is tryng it for tinnitus relief, but if all fail (Tegretol/Trobalt) you can use it safety because it hasn't the serious side effect of Trobalt and Tegretol. Request time... but probably it will work.

Forget Gabapentin... reduce the doses and then throw it away

with all my heart I hope you will soon find the relief you deserve

Best wishes

 

Thank you for the very detailed suggestion. However: My real problem began after exposure to loud noise (burglar alarm) for at least a minute without covering my ears. I did have T before that, but it was not that bothersome. Perhaps it worsened, perhaps I have a combination of problems now.

I am thinking of going through a couple of further exams to verify whether the problem lies in the cochlea or the nerve. Thinking of auto acoustic emissions and ABR to verify cochlea and nerve problem accordingly. I just found one (!) doctor who does such exams and plan to visit him. But he also promotes laser therapy, which makes me skeptical since this LLLT therapy is believed to be scam by many.

I am really hopeless here in my country, visited many ENTs who treat me like a casual cold or flu case, some of them didn't even bother looking into my ear! Though I really do not need another ENTs exam, but an audiologist or neurologist one. Finding that is REALLY difficult, the problem of Tinnitus in my country is confronted like an extraterrestrial one, with the only common conclusion of ALL doctors: Let it be and put trust in your organism. My audiogram does fall above 6000Hz (my T is in high frequency) which makes them treat it as I have a natural hearing! My hyperacusis is also ignored by doctors completely!

Perhaps they are talking about habituation. Now, if the problem lies in acoustic trauma, perhaps habituation is the only hope, until a new medicine is ever found (although this situation cannot be endured until then! ). But there is an MRI that shows sings of mvc, and the fact of Tinnitus signs present before the alarm incident. The fact that I wasn't bothered that much before is crucial though... Perhaps mine is a combo problem!

Does Keppra help in mvc? Who knows... Does it give immediate results? Again who knows... Is tegretol preferable? Does Tegretol help in acoustic trauma? Again who knows. Trobalt? Acquiring it is tricky and about mvc, again WHO knows!

The only positive conclusion is that Neurontin does not help. After 1 month it would be useless to carry on with it, even if my doctor suggests it!

It is now 3 and a half months of my acoustic trauma incident, and about 6 months or more that I experienced ear problems (fullness) and a less bothersome T (the possible mvc). Perhaps there are time windows. For example the mvd surgery requires having the problem for less than 3 years the most...

Now how would you go on from that?

 

Yeas, unluky (and it is not only my experience/opinion) LLLT does do exactly nothing. It is all suggestion.
Now the dilemma: tinnitus after exposing to loud noise and MRI scans who shows the NVC.
You have still more possibility of relief, Do not despair. Very often to find the right way, it takes time. Be stubbornly patient. Do you have hearing loss???

If nvc is the responsible of yur tinnitus ou will hear the difference with the tegretol 200mg 1 pill at morning, and if it loose efficacy after 1 month, you have a reason to write an email to Dr. Vanneste in Belgium with your story...because there is not only dangerous surgery NVC but Vagus nerve stimulation. Be clear, VNS is under investigation but more promising in the treatment of refractary epilepsy, tremors, and tinnitus (UNILATERAL PURE TONE TINNITUS)

About VNS:

http://www.ncbi.nlm.nih.gov/pubmed/24255953

http://www.ncbi.nlm.nih.gov/pubmed/24309259

http://www.ncbi.nlm.nih.gov/pubmed/23099209

and more others on: http://www.ncbi.nlm.nih.gov/pubmed/?term=vagus+nerve+stimulation+tinnitus

About Tegretol;

http://www.ncbi.nlm.nih.gov/pubmed/20360168

http://www.ncbi.nlm.nih.gov/pubmed/16514262

Consider that "lucky" you are still not cronic and i pray that one day not far, you will wake up without tinnitus.

In my final opinion you must remove Gabapentin...make 2 week of complete wash-out and then try Tegretol!

This is what I would do. Does not mean you have to listen to me. I'm not a doctor so I'm not reliable. You can be the best doctor of yourself because you know suffering.

Best wishes