Levetiracetam (Keppra) — Another Possible Potassium Channel Modulator?

Discussion in 'Research News' started by Viking, Dec 15, 2014.

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    1. Viking
      No Mood

      Viking Member Benefactor

      Location:
      Italia
      Hi friends;
      as you know i'm waiting for the Switzerland appointment with Dr. Jeanmonod.

      Waiting for it, my tinnitus and headache are out of control, and my neurologist keep me on Keppra (Levetiracetam). This is an anti-seizure drugs with a potential act on potassium channel without the serious side effect that i have experienced with Retigabine (Trobalt) and Flupirtine (Efiret).

      I'm on first day, I'll update you.

      Has anyone tried it?

      I have also found this paper: http://www.sciencedirect.com/science/article/pii/S002839080300248X

      Reduction of voltage-operated potassium currents by levetiracetam: a novel antiepileptic mechanism of action?

      Abstract
      Levetiracetam (ucb L059; Keppra™) is a novel antiepileptic drug. Its effects on action potential generation and voltage-operated potassium currents were studied in acutely isolated hippocampal CA1 neurones from rat and guinea pig, using the patch-clamp technique in the whole-cell configuration. (i) Levetiracetam reduced repetitive action potential generation and affected the single action potential. Levetiracetam, 100 μM, decreased the total number of action potentials and reduced the total depolarisation area of repetitive action potentials by 21%. Furthermore, levetiracetam increased the duration of the first action potential slightly, prolonged that of the second action potential by 13% and decreased the slope of rise by 23%. (ii) Levetiracetam decreased the voltage-operated potassium current. Without effect on sodium and A-type potassium currents, levetiracetam, 100 μM, reduced the delayed rectifier current by 26%. The concentration of half-maximal block was 47 μM for guinea pig and 6 μM for rat neurones. Thus, the reduction of repetitive action potential generation by levetiracetam can be attributed, unexpectedly, to a moderate reduction of the delayed rectifier potassium current, as supported by a simulation of action potential generation. This suggests that a reduction of potassium currents may contribute to the antiepileptic effect(s) of levetiracetam.


      Best wishes
       
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    2. Viking
      No Mood

      Viking Member Benefactor

      Location:
      Italia
      Specific for kv 3,1
      http://www.ncbi.nlm.nih.gov/pubmed/20065495

      J Physiol Pharmacol. 2009 Dec;60(4):37-47.
      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.
      Huang CW1, Tsai JJ, Huang CC, Wu SN.
      Author information
      • 1Department of Neurology, National Cheng Kung University School of Medicine, Tainan, Taiwan.
      Abstract
      Levetiracetam (LEV) is an S-enantiomer pyrrolidone derivative with established antiepileptic efficacy in generalized epilepsy and partial epilepsy. However, its effects on ion currents and membrane potential remain largely unclear. We investigated the effect of LEV on differentiated NG108-15 neurons. In these cells treated with dibutyryl cyclic AMP, the expression level of the K(V)3.1 mRNA was elevated. With the aid of patch clamp technology, we found that LEV could suppress the amplitude of delayed rectifier K(+) current (I(K(DR))) in a concentration-dependent manner with an IC(50) value of 37 microM. LEV (30 microM) shifted the steady-state activation of I(K(DR)) to a more positive potential by 10 mV, without shifting the steady-state inactivation of I(K(DR)). Neither Na(+), nor erg (ether-a-go-go-related)-mediated K(+) and ATP-sensitive K(+) currents were affected by LEV (100 microM). LEV increased the duration of action potentials in current clamp configuration. Simulation studies in a modified Hodgkin-Huxley neuron and network unraveled that the reduction of slowly inactivating I(K(DR)) resulted in membrane depolarization accompanied by termination of the firing of action potentials in a stochastic manner. Therefore, the inhibitory effects on slowly inactivating I(K(DR)) (K(V)3.1-encoded current) may constitute one of the underlying mechanisms through which LEV affect neuronal activity in vivo.
       
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    3. Champ
      Woot

      Champ Member Benefactor Team Tech

      Location:
      Boston, MA
      Tinnitus Since:
      1/2013
      Cause of Tinnitus:
      Acoustic trauma from headphones
      Interesting. So which Kv channels does Autifony open again? Is it the same as this one?

      What do the number designations indicate... what does the 3 and 1 mean?

      I wish you luck comrade.
       
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    4. Viking
      No Mood

      Viking Member Benefactor

      Location:
      Italia
      yes mate. Is the same potassium channel who is in the Autifony target!

      The number indicate the specific sub-unit of the potassium channel
       
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    5. dan
      Chatty

      dan Member

      Tinnitus Since:
      06/2011
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    6. Danny Boy
      Cheerful

      Danny Boy Member Benefactor Hall of Fame

      Location:
      England
      Tinnitus Since:
      7/2014
      Cause of Tinnitus:
      Ear infection
      So this targets the KV3 channels? Is this easier to get than trobalt on the NHS?
       
    7. Viking
      No Mood

      Viking Member Benefactor

      Location:
      Italia
      Yes. More much easy. Is not under drug vigilance and with minor side effect. I'm experiencing only drowsiness
       
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    8. Danny Boy
      Cheerful

      Danny Boy Member Benefactor Hall of Fame

      Location:
      England
      Tinnitus Since:
      7/2014
      Cause of Tinnitus:
      Ear infection
      Ok, I'll see if I can get some! So this for sure targets the KV3 channels? So there is a drug like Autifony's out there!?
       
    9. xanaxvictim

      xanaxvictim Member

      Tinnitus Since:
      10/2014
      Cause of Tinnitus:
      Xanax
      And effect on T when compared with RTG?
       
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    10. Danny Boy
      Cheerful

      Danny Boy Member Benefactor Hall of Fame

      Location:
      England
      Tinnitus Since:
      7/2014
      Cause of Tinnitus:
      Ear infection
      Who wants to bet my doctor won't give it to me?
       
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    11. Viking
      No Mood

      Viking Member Benefactor

      Location:
      Italia
      Same effect. Lowering without spike. I don't want to create alarmism but this drug is feeling good for tinnitus and side effect.
      I'm on 500 morning + 500 evening.
      There are more papers about the use of this anticonvulsant for the tinnitus management in germany,poland and France
       
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    12. Viking
      No Mood

      Viking Member Benefactor

      Location:
      Italia
      Why not? It is also a mood stabilizer. If you are able to take trobalt (a very hard drug)....Keppra is a "coffee"
       
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    13. Carlos1

      Carlos1 Member Benefactor

      Location:
      Boston
      Tinnitus Since:
      08/2013
      Cause of Tinnitus:
      Root Canal
      Hello Viking just read the side effects and one of the side effects of levetiracetam is Tinnitus
       
    14. Viking
      No Mood

      Viking Member Benefactor

      Location:
      Italia
      Yes i know in my experience, like you, I realized something: Many medications can cause tinnitus. But if you already have tinnitus can happen otherwise...
      On my leaflet there isn't tinnitus as side effect!
      Probably is a legal protection of FDA like many medications
       
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    15. nogood
      Torn

      nogood Member Benefactor

      Tinnitus Since:
      04/2014
      Cause of Tinnitus:
      ototoxicity/infection
      Hi @Viking please do keep updating
      if it does work it will be great news.
      so far i can't track down if the RTG is available in india or not, i guess most probably not.
      But this levetiracetum is available is surly can get my hands on this one.
      if it shows good results i will give it a try in Feb (i will be back to India in feb)
       
    16. tom1989

      tom1989 Member

      Tinnitus Since:
      11/11/2014
      It always seems that proposed drugs for T actually cause T!!
       
    17. Manuel Tissm
      Angry

      Manuel Tissm Member

      Location:
      Portugal
      Tinnitus Since:
      07/2014
      Cause of Tinnitus:
      Acoustic trauma
      The portuguese leaflet there isn't tinnitus as side effect.
      Go @Viking . You are the new hope for all of us!!!
       
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    18. Viking
      No Mood

      Viking Member Benefactor

      Location:
      Italia
      In fact i don't found on google or pubmed the realtionship between keppra (levetiracetam) and tinnitus. Only on epilepsy forum someone experience tinnitus in politherapy and with very higher dosage. My neurologist knows me well. He knows my adventure with Trobalt as well as many other medicines that we tried. I do not think that would give me a drug further damaging to my debilitating tinnitus.
       
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    19. xanaxvictim

      xanaxvictim Member

      Tinnitus Since:
      10/2014
      Cause of Tinnitus:
      Xanax
      Many A/D and tranquilizers can cause T, yet ironically they are frequently prescribed to T sufferers to help them cope with the situation. It is well understood that withdrawing from benzo can cause T and H (look at benzobuddies to see all those poor souls who got T and H due to benzo withdrawal).
       
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    20. Viking
      No Mood

      Viking Member Benefactor

      Location:
      Italia
      Dear friend i agree and know by 8 years the frustration. I have not found anything (there are no miracles). I'm just saying that maybe there is a less risky alternative to other similar drugs such as Trobalt.
      yes i know! i have tryed the impossible in 8 year. Only 1 example: amytriptiline...an old TCAs...for many people is a miracle for migraine and tinnitus...for others is a nightmare!
       
    21. lapidus

      lapidus Member

      Location:
      Sweden
      Tinnitus Since:
      1999
      Cause of Tinnitus:
      Noise induced
      In the swedish leaflet there was no mention of T as a side effect either.

      This is pretty interesting @Viking I wish you all the luck in the world.

      What do our science people say about this one?
      @jazz
      @locoyeti
      @rtwombly
      @attheedgeofscience

      I really wish @benryu would come back and shine some light on this.
       
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    22. dan
      Chatty

      dan Member

      Tinnitus Since:
      06/2011
      @Viking - how is it going on Keppra ? any similar effect on T as Trobalt ?
       
    23. Viking
      No Mood

      Viking Member Benefactor

      Location:
      Italia
      Is too early to know. My tinnitus is more unstable and reactive. I've noticed only the small side effect and no spyke when i use the car. Usually (ever) after i take the car and drive my T became slowly loud. Today not. but it could be a placebo.
      i think are necessary 1 or 2 week to estabilish how and if it work.
      i hope...
       
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    24. xanaxvictim

      xanaxvictim Member

      Tinnitus Since:
      10/2014
      Cause of Tinnitus:
      Xanax
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    25. Danny Boy
      Cheerful

      Danny Boy Member Benefactor Hall of Fame

      Location:
      England
      Tinnitus Since:
      7/2014
      Cause of Tinnitus:
      Ear infection
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    26. Juan Carlos
      Whistles

      Juan Carlos Member Benefactor

      Location:
      Spain
      Tinnitus Since:
      02/2014
      thats good news, what dosage are u taking @Viking ? whats the maximum dosage? I guess taper up is also recommanded
       
    27. xanaxvictim

      xanaxvictim Member

      Tinnitus Since:
      10/2014
      Cause of Tinnitus:
      Xanax
      Tinnitus? The medical community doesn't even give a shit
      They tell you to go for an MRI and if there's no tumor they tell you there's no cure learn to live with it it's not going to kill and then kick you out of the clinic or better tell you to listen to Goddamn white noise for the rest of your life. Hell, like visual snow sufferers we can't even get a proper diagnosis, some ignorant doctors even believe it is an imagined condition if your scan came back clean you're alright without any problem.
      The scientific community? There are a few of the scientists who are really working on it, but no funding! They're working tirelessly towards a functional and molecular understanding of this shit but they face constant shortage of research funding. T sufferers are abandoned by the world, betrayed by the world. Why? Because no one give a shit and no one think it's a real problem. What they know is you can eat, breathe, move, and they believe whatever your condition is it's mild and doesn't really matter. You tell doctors your sufferings they label you as "Depressed", "Anxiety Disorder" (in my opinion Anxiety is really an imagined medical condition marketed by big pharma) and put you on more addictive and ototoxic drugs.
      Not to mention I got this sh.t from those Goddamn psychiatrists and psychiatric drugs. They were supposed to help me but I end up losing my health and my life. Those who are responsible will never need to pay for it, pay for all my sufferings. This damned world has no justice.
       
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    28. Martin69
      Artistic

      Martin69 Member Benefactor

      Location:
      Germany
      Tinnitus Since:
      10/2013
      Cause of Tinnitus:
      (Health) Anxiety
      @Viking
      Please keep us updated how it affects your T. Levetiracetam UCB is available in Germany.
      Tinnitus is not listed as side effect.
       
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    29. Viking
      No Mood

      Viking Member Benefactor

      Location:
      Italia
      The good news is that instead the trobalt, this drug, if is effective, don't need dangerous dosages. I'm on 500 morning + 500 evening. Is important to gave 8 max 12 hour between first and second pill. Max dosage i will go on next week is 1500mg. 750 morning 750 dinner. I'm no hoping for a CURE. I want to be clare. I am only trying to bring back tinnitus at previous level before hearing aids worsenend
      Best wishes
       
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    30. Viking
      No Mood

      Viking Member Benefactor

      Location:
      Italia
      But infact i don't know why people say that Keppra cause tinnitus. Never in "not common" - "rare" - "unknow" side effect...
      I want to be clear with all because we are all friends. I'm testing only a drug...i'm not a "seller" of false hope. I SUFFER
       
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