Brivaracetam — KV3.1 Modulator

Birdman SOUNDTRACK - Main Theme (Flying Suite)

 

So wait, you do have hyperacusis? Or don't you? Do you have reactive tinnitus?

 

cool, if you've run out of rebuttals maybe you can answer my question from a few posts back:

@Geo , I'm going to reply to you again not because I want to argue, but because your first post made me so angry that someone would downplay the intensity of my tinnitus or distress that I lost my ability to empathize and barked at you instead of trying to find some common ground. I sincerely apologize.

Well, 'anxiety' isn't really useful here because it generally implies a psychological thing, and I don't think that's accurate because tinnitus is a physical/electrical thing that we can see with fMRIs and stuff. But, there's pretty good evidence to suggest that the transmitter systems and brain structures involved with tinnitus intensity and distress, are the same transmitter systems and brain structures that are involved in what we call "anxiety disorders". I'm not big ob psych labels in general, for one thing they lead to dumb sematic arguments like this one.

That said, when I have been most severely hyperacoustic, I have also been absolutely out of my mind with anxiety. But, I don't take that as a sign that the anxiety causes the audio glitches, or even that the audio glitches cause the anxiety per se -- I think they are both evidence of hyperactivity in related parts of the brain.

Don't worry, I didn't say that and I certainly wouldn't. All I said was that I don't think it's as bad as terminal cancer or AIDs, and my reason for saying that is I'd just gotten through getting somewhat over having my life upended by tinnitus and benzodiazepine withdrawal for years when I was unfortunately forced to watch one of my close friends dying of cancer, horribly and painfully, and those images are burned into my head forever. If someone had said "I just watched my close friend/family member die horribly of one of the worst most aggressive kinds of cancer, and let me tell you, that's a walk in the park compared to my tinnitus" then I would have looked it the post differently, but that's not something I've read ever in 15 years of reading about tinnitus on the internet, and I would find it shocking and terrifying.

 

At this point I would say that the extent to which I am hyperacoustic is within the realm of normal human experience, given that I am able to do things like drive cars (and motorcycles, with earplugs) and listen to music and be in restaurants in public. However, this has not always been the case.

My tinnitus still reacts in an obvious and significant way to certain kinds of audio exposure, and this does impact the way that I live my life to a degree that I don't really know anyone else in the same situation; I never leave home without earplugs, and I frequently wear them in situations when other people do not. One thing that I've noticed which is really odd, is that when I put plugs in these days, unless I am already in a state of stress, the tinnitus is actually easier to not spend time thinking about. I think this is because on some level, any time I'm in an environment which even partially masks my noise, some part of my mind is still fixated on it and trying to seek it out and amplify it. Once I put the plugs in, the tinnitus is completely impossible to mask even partially, and so that part of my brain relaxes and says "oh, cool, I can hear it clearly and I know I can hear it clearly, so I can stop wondering whether or not I can stop wondering if I can hear it clearly and focus on whatever I'm thinking about". Part of me has actually wondered if wearing plugs 24/7 for a period of time could sustain that effect and maybe help rewire the parts of my limbic system that still want to focus on the sound. I have stopped short of doing that because my research into the effects of wearing plugs 24/7 for a period of time, makes me think that I'd be mucking with things to a pretty significant level. That is, I do not think it's impossible that plugging 24/7 might encourage some kind of cortical map changes, but I'm not at all convinced that they would necessarily be desirable changes, and if they were not, they might be hard to unwind.

So, yeah, I still think about this stuff a lot! I don't let it run my life the way I used to, though, and the times that I'm not thinking about it, my life often feels rich and full and happy. I am also often able to think about tinnitus somewhat critically and not immediately get depressed and anxious about it, which is more than I can say for what my life was like a few years ago.

By the way, if you had asked me this same question not that long ago, I might have replied "I have absolutely horrendous hyperacusis, I am in physical pain on a regular basis from exposure to routine sounds, it has gotten hard for me to travel or be around any kind of noise, and if I hear too many loud noises, my ears ring horribly for days and it makes me seriously contemplate suicide". That would have been true, too, but very thankfully, it is not true today.

 

So if your hyperacusis/reactive tinnitus was so bad, why don't you try keppra? Do you like suffering? Or is that me being foolish?

 

If I had known about Keppra a couple years ago, I definitely would have tried it. God knows I tried a bunch of things which were a lot less safe.

If I were at the future for some reason unable to maintain my current level of functioning and happiness, I also might take a crack at Keppra. But, it's a heavy hammer, and I'll leave it for a bigger nail than the spike I've got through my ears right here in this moment today.

 

Then why don't you try it now? It's cheap, safe and effective. It's worked on me, viking and many others. So why won't you try it, if yours is so bad? Are you scared of a mild headache?

 

Nope, and if a headache was the worst side effect I could find reliable reports of, I still might try it! Psychosis scares me a bit more, though.

I don't know if maybe you're not really reading everything I said; I think I've made it pretty clear that I'm not taking Keppra now because I've found other ways to deal with life for the moment. Literally most of the time that I've spent thinking about T&H today has been butting heads with you on here. That doesn't mean it's not been there all along, it means that I spent my afternoon piecing together a piece of software, and I just don't fucking have time and energy to think about two things at once. The software pays my bills, the tinnitus is just a pain in the ass, which one do you think I should spend my time on?

Don't tell me that your tinnitus is so bad that you'd never be able to do anything in spite of it, because you've been on here with me all afternoon writing sentences in english. You're literate, and you express yourself pretty well. If you can do that, then you can write code no problem, if anything computers are a lot easier to deal with because you never have to tell them the same thing over and over in slightly different ways to get it across.

 

I hate to see such bickering on this site. Everyone here has his or her own level of suffering. We can learn from each other's experience, strength, and hope. Let's celebrate our differences, as well as our similarities. We all have tinnitus -- no matter severity, cause, or form -- or else we wouldn't be here. This is a support forum above all.

 

Hyperacusis is not about thinking about it? Do you know what hyperacusis is? It's where noises are overly amplified so noises hurt us, we are more sensitive to noises. If you can block out hurtful noises I'd like to hear about that one, no pun intended. Anyway, if you're not willing to try keppra a safe drug then you're either foolish or someone with it mildly. Now, geo here has serious hyperacusis and is desperate and is going to try keppra...Why? Because it affects his life to where it's destroying it, can you understand that? The solution? A simple drug, a generic drug, given to babies and dogs. Keppra can help yet you don't want to? Sorry, I don't buy it. If you don't want to try these drugs which can help you, why are you here? What's the point? If you're not here contributing to offering solutions to real problems, then what is the point? I'm here, offering real solutions not some poncey white noise generators, TRT or some illusion or trying to make the issue not there. I'm not a magician, I'm a realist.

 

Im a witness T can be a killer. I cant sleep three years running. I now have gastritis and ulcers. I cant eat.
Im suffering. I now have Hypothyroid. Ive seen a series of awful doctors The anxiety is more like torture.
I lost my job the girl I loved. My body aches all over. I cant live this way. I want to live so badly but yet this life is not working now. I was blessed for most of my life. A 15 year law suit from my wealthy sister has destroyed much.
She is very wealthy but she has to have inheritance that doesnt belong to her. Greed is the essence of death.

 

Well she Owes you a HIFU treatement to say the least ! tell her sorry, I love you, I need help ... Whomever was worng or right ... Or if you have 36000 euro I would fly to Switzerland tomorrow!

offtopic btw

 

Hey, can you please show me where it says Brivaracetam is Kv3.1 cause the woman I spoke with from the company says its not ... i asked you in an other post before with back up info on it.

 

It's not a K+ channel inhibitor.
Both levetiracetam and brivaracetam target the decreased excitation of the Synaptic vesicle glycoprotein 2A (SV2A).
This has been pointed out by @NGC891 's very useful post (link) and there is also a mention on this wikipedia page.
Doesn't mean it's useless though...

 

So, no Kv3.1 for Brivacetam or Keppra? The only one that currently uses Kv3.1 is Retigabine? And, of course, the far away Autifony?

 

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

Levitiracetam decrease SV2A excitation but also seems to act on KV3.1...

"Levetiracetam (LEV) is an S-enantiomer pyrrolidone derivative with established antiepileptic efficacy in generalizedepilepsy 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 KV 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 μM"
" 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."

 

I completely agree with Geo mild T is a walk in the park, you can still go about your life the same way. Now with severe T its a different story and adding H to the party is even further catastrophe. Just as Geo said EVERYDAY is a struggle for us severe T and H sufferers, just being in the house isn't safe, I stay in a quiet room all day to try and recover whatever the hell recent spike I got. Now that summer is coming we gotta watch out for even more terrifying sounds, this is a very draining situation, and we live like hermits in a shell to try and protect ourselves but thats not even enough, because loud sounds are unavoidable, its everywhere...... All we can do now is be hopeful that a treatment or cure comes out soon to get out of this living nightmare, even if it just lowers are T that would be relief!!

 

“Brivaracetam (BRV) is a pyrrolidine derivative currently being investigated for the treatment of epilepsy (Bialer et al., 2010). It is a novel high-affinity synaptic vesicle protein 2A (SV2A) ligand (Kenda et al., 2004; Gillard et al., 2011). Preclinical studies demonstrated efficacy in a wide range of animal models of partial-onset (focal) and generalized seizures (Matagne et al., 2008) and a higher affinity (>30-fold) for SV2A in human cerebral cortex compared with levetiracetam (LEV) (Gillard et al., 2011)”.

Ligand
From Wikipedia, the free encyclopedia
This article is about ligands in inorganic chemistry. For ligands in biochemistry, see Ligand (biochemistry). For other uses, see Ligand (disambiguation).


Cobalt complex HCo(CO)4 with five ligands
In coordination chemistry, a ligand (/lɪɡənd/)[1] is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from covalent to ionic. Furthermore, the metal-ligand bond order can range from one to three. Ligands are viewed as Lewis bases, although rare cases are known to involve Lewis acidic "ligand."[2][3]

Metals and metalloids are bound to ligands in virtually all circumstances, although gaseous "naked" metal ions can be generated in high vacuum. Ligands in a complex dictate the reactivity of the central atom, including ligand substitution rates, the reactivity of the ligands themselves, and redox. Ligand selection is a critical consideration in many practical areas, including bioinorganic and medicinal chemistry, homogeneous catalysis, and environmental chemistry.

Ligands are classified in many ways: their charge, their size (bulk), the identity of the coordinating atom(s), and the number of electrons donated to the metal (denticity or hapticity). The size of a ligand is indicated by its cone angle.

 

I will disagree, when I first got T 25 years ago, it was mild, I could only hear it at night and it sounded just like silence sounded when it gets loud, as soon as I got up and into my daily routine It was like I never had it, couldn't hear it during the day!

To someone like me, who use to love walks in the country or staying up till late so I could go to bed when the traffic stopped driving past outside just to listen to the dead silence and solitude of the night.

That was my paradise, It was something I loved to do, almost like a hobby that's how much my silence meant to me!

So my reaction to mild T was bad, I would spend many nights crying myself to sleep, I was suicidal wishing that I would go to sleep and not wake up.
It was no walk in the park for me, I can tell you.

Even mild T to someone like myself who's part of their reason for living was enjoying silence is devastating!

 

@RichL well varies with every person.. But like stacy says i also have very severe T and mine just like hers worsens with everyday sounds idk why but it does were just very unlucky.. But when i got mild t it was hard at first because ur not use to a little noise in ur head..but in time i got use to even the couple of permanent spikes between two years.. But ever since my bad h came it just keeps worsening the t.. Keeps upping volume and changing ans increasing tones.. It is ridiculous if you hear what we hear and go through daily . You would understand by what we mean about mild t being a walk in the park..i wish i had mild just like 90% of t sufferers. But now i hear a bad playing band in my head very loudly everysecond and have to watch out for sounds as it just makes them play louder..

 

Ive never contemplated suicide till these months now its too much .. I really hope keppra works and fades this bad h as the reason to all my problems my T bever acted like this before but even if it cures it my Horrid t will stay..

 

I can relate to that as in the past year I, like you, have bad H and reactive T, way louder than it used to be.

Yes in that respect I agree that looking back, when I did eventually habituate to mild T, compared to what you, I and by the sounds of it Stacy have now, mild T does seem like a walk in the park!

 

@RichL yes thats what i ment.. Mild t is still awful to people that cant accept it but thats what it is acceptance at first as i did took me a while but after that the little noise was like watever i would sleep fine... But after 100 spikes later some permanenr some come and go its like for real man what the heck this isnt right and most have come from this H and also its my neighborhood i livee in a loud ass community..Most of my spikes have came from my house thats how noisy it is here i wish i lived in a ranch were i hear quiet and relax my ears but i cant here. Tomorrow im getting a noise reducing window installed in my room.. And having my loud ac moved to the other side of the house it bugs my H so much.. Even my mother has offered to find me a apartment and keep me there so ill let my ears rest in silence for a change but i am not dependant on my own right now i need assistance for everything..

 

With mild t and no h still had my life.. Worked , and enjoyed life with a couple of limitations..

 

I agree but everything is relative...

 

Who else has keppra worked for....besides you and @Viking ?

 

Update from Viking!

"Small update;
the doctor who prescribed the Keppra on me in december of past year, it being administered to patients who had previously received some relief from the combination of gabapentin + clonazepam. The results seem to be encouraging, especially in the group of patients who suffer from tinnitus unilateral not tonal but white noise, narrowband noise linked with Misophonia or hyperacusis. After 3 months of testing, the maximum dosage of 2000mg per day were obtained the following results:
1) Reduction of tinnitus NOT TONAL from 6 to 3. Disappearance of "tinnitus reactivity". Disappearance of Misophonia (FULL).
Drastic reduction of the headaches associated with iperacusia.The patients have improvement in mood and in their ability to react to their situation of suffering. 2 persons have abandoned the use of SSRIs and are climbing out the use of benzodiazepines.
2) If the tinnitus is tonal, no relevant difference. (not lucky people)
3) If there are hyperacusis or Misophonia, after a month of treatment, the symptoms begin to weigh less on quality of life.
4) In patients who did not obtain benefits, was prescribed the Flexiban (Flexeril ... always cyclobenzaprine), with good results on tinnitus tonal, general tension, hyperacusis and headaches. It is noted that these patients have problems related to the neck or jaw or to the structure of the dental arches. Very common side effects that lead patients to abandon the following therapy are excessive sedation or tachycardia. Flexiban has a structure similar to Tegretol. Both are "cousins" of tricyclic antidepressants such as amitriptyline or nortriptyline that already in the past have been shown to have some efficacy in the tensive states, headaches or migraine, hyperacusis, generalized anxiety.
It is hoped that these results are permanent, in view of a future development of Biviracetam (enhanced version of Levetiracetam x10) who @Danny Boy is most active in the research, the suffers may have some help with a drug already tested and without serious side effects, avalaibilty and low price."

 

I have read many of your posts Danny Boy, and I think I love you. But don´t be alarmed. It´s a non-sexual crush.

I just think the way you are providing information, the way you respond to people and being positiv about any remedies for our terrible T. is amazing.

Im just happy that I found this forum and that I found you here. Thank you!

Man, 42, Oslo, Norway.

 

I have a dumb question. What is tonal tinnitus by definition?

 

Hearing a single tone or tones, fleeting T is usually tonal unlike cicada's, buzzing, whirring, clicking and then their's pulsatle which is a whoosh sound in time with your heart beat.

IMO there's no such thing as a dumb question!