Christian78
Member
- Dec 17, 2013
- 965
- Tinnitus Since
- (Sep 2013)
- Cause of Tinnitus
- progressive tinnitus, time of expiring in next 3-6 months
this means eve i used drug stronger dosage t return to high level.I think he meant that his T went down but went up again to it's original level when the drug wore off.
this means eve i used drug stronger dosage t return to high level.
Thanks for the advice. Tonight I'll take the Trobalt and before going to sleep 1mg of rivotril instead 2mg. I contacted a neurologist experienced enough and told me that the "wash out" the benzo is doable in a week. I'll try. If then goes wrong, I always close at hand.Hey @Viking don't drop that benzo too darn fast!!! It can really trigger big time 'feci' like anxiety and so on. Plus it may well have an impact on your tinnitus as they do tend to calm it somewhat for a lot of us.
Slow is safer with BOTH these drugs!!!
Take care...(and my morning coffee is really wearing out. This retig' thread & research is too darn addictive and bad for my chores list!) Zimichael
I would take it easy on the clonazepam cutting buddy.Thanks for the advice. Tonight I'll take the Trobalt and before going to sleep 1mg of rivotril instead 2mg. I contacted a neurologist experienced enough and told me that the "wash out" the benzo is doable in a week. I'll try. If then goes wrong, I always close at hand.
I agree with you. I consider it a major factor ... as Trobalt me great sedation, taking it in the evening I could catch a double chance. Trobalt would work at night when chemical changes occur in the brain also helping me to sleep. The Rivotril I took him to sleep but it has completely lost its effectiveness. After 8 years ... I think it's normal. I was starting to use it during the day and I immediately stopped to avoid ending up like a junkie. I could get a double result. is not a matter of impatience! What do you think?I would take it easy on the clonazepam cutting buddy.
I understand a certain impatience and wanting to get off of it quickly, but with benzodiazepines, slower is almost always better. Try taking off .25 mg a week at a time and see how you do there. It's a much better scenario than cutting 1 mg at a time from a total of 2mg (that's half your entire dosage!). Clonazepam has a stupidly long half life as well, so you won't notice the cuts probably until a few days after you have cut. Then, it could be a really crappy time. However, I support anyone who wants to stop taking a benzo, and if you have the ability to cut that much that fast with minimal side effects then more power to you man.
I agree with you. I consider it a major factor ... as Trobalt me great sedation, taking it in the evening I could catch a double chance. Trobalt would work at night when chemical changes occur in the brain also helping me to sleep. The Rivotril I took him to sleep but it has completely lost its effectiveness. After 8 years ... I think it's normal. I was starting to use it during the day and I immediately stopped to avoid ending up like a junkie. I could get a double result. is not a matter of impatience! What do you think?
Thaks
Ivan
Huh, I have that too (typewriter thing). Maybe my ears are jammed up from wearing ear plugs. Scared to touch them these days so I just leave them alone. Maybe I will attempt a clean.Ivan and Christian both have had tinnitus longer than Matt, so it's not a big surprise if it takes longer for them to see results. Just hope you do, gents.
Great post on effects, benryu. I still get confused by the different terms, though. Is KV3 one or a family of channels? Is it in the range that retigabine affects or separate?
I was wondering if the effects of retigabine could make someone less likely to respond to AU00063, but from your post, there doesn't seem to be any reason this would happen.
Tomorrow at 1pm EST I'm scheduled to arrive at a new neurologist's office to fill out paperwork ahead of our 1:30 appointment. I mean to ask him for a 3-month prescription, which I can obtain for an $80 co-pay provided I fill it by Thursday midnight. I'm used to pill cutting, so I'll ask for the 300 or 400mg dosage. That way I should be able to dose up 100mg at a time and really stretch the supply.
I'm not totally sure I want to be a guinea pig, but I have to get the pills now or never. If I'm successful, I mean to do more research and consult with the doctor before I take the first pill. If Autifony posts their inclusion criteria for the US trial and it looks like I'll qualify, I may well wait for September. This, of course, I say while my right ear is just barely whistling....
Almost forgot. I had a strange experience of typewriter tinnitus today. I've not had that regularly. It was very distinctive and odd. Since it's not one of my usual noises, I checked my ears for wax and sure enough, they were pretty well plugged. I used my cleaning loop to get them as open as I could and the typing is pretty much gone. Thought I'd post this in case Viking, like me, has been avoiding Q-tips since diagnosis. I think I'll do a coconut oil cleanse tonight and really get the gunk out!
Sorry it's some sort of double post, but I think this information is as relevant for the Flupirtine thread than the Retigabine Thread.
I see many questions about the drugs acting on potassium channels.
Here is a technical but clear view on some of those drugs. (Flupirtine, Retigabine, AUT00063)
First and most importantly, potassium channel modulators should not be compared, there is a ton of parameters and subtilities that can change drastically the impact of one drug.
Flupirtine acts mainly on the Kv7.3 , retigabine specifically acts on the neuronally expressed KCNQ2-KCNQ5 (Kv7.2-Kv7.5) channels, AUT00063 will act on the Kv3 channels.
Talking from a neuronal perspective, Kv7 and Kv3 mediate the channels and more precisely the action potential.
The action potential is an electrical signal generated near the cell body of a neuron that propagates along the axon to the axon terminals.
After an acoustic trauma, or after taking some drugs such as quinine there is an interference with the excitability of spiral ganglion neurons (The evil glutamate is guilty ). The membrane potential changes and the modification of the action-potential waveform induced by the problem put the individual in a T. state.
Going back to the potassium channels, Kv7 channels primarily control the interspike interval with a limited effect of the repolarization. Kv3 channels control the repolarization of the action potential and are expected to induce a new state.
The idea is to open the right channels to lead to a neuronal hyperpolarization, thereby stabilizing the membrane potential and decreasing excitability.(No or very little Tinnitus)
Conclusions:
- Despite a drug being potassium channel opener, it has to be very precise to work.
- Flupirtine doesn't act on any sub unit related to T. ( So no possible impact)
- Retigabine acts on interspike interval, meaning less T. spikes and it can possibly repolarize the action potential for some people. But the sub unit range is too wide with numerous side effects. (so it can work to stabilize T. and decrease it to some extent, but is not specific enough to be viable.)
- AUT00063 acts directly on the repolarization and is much more precise, so it's a viable solution providing it works as expected
Thanks ben, very good read. Reasonably explains why Trobalt can still benefits T and yet not fully.
It could well be that Kv3 channels are the root cause of all T regardless of etiologies. Noise trauma, injuries, blood circulation, TMJ and etc etc all ultimately lead to abnormal Kv3 channels!? Hope so!
Really informative and fascinating post. I hope you are right about these channels. Maybe you should work for Autifony?Sorry it's some sort of double post, but I think this information is as relevant for the Flupirtine thread than the Retigabine Thread.
I see many questions about the drugs acting on potassium channels.
Here is a technical but clear view on some of those drugs. (Flupirtine, Retigabine, AUT00063)
First and most importantly, potassium channel modulators should not be compared, there is a ton of parameters and subtilities that can change drastically the impact of one drug.
Flupirtine acts mainly on the Kv7.3 , retigabine specifically acts on the neuronally expressed KCNQ2-KCNQ5 (Kv7.2-Kv7.5) channels, AUT00063 will act on the Kv3 channels.
Talking from a neuronal perspective, Kv7 and Kv3 mediate the channels and more precisely the action potential.
The action potential is an electrical signal generated near the cell body of a neuron that propagates along the axon to the axon terminals.
After an acoustic trauma, or after taking some drugs such as quinine there is an interference with the excitability of spiral ganglion neurons (The evil glutamate is guilty ). The membrane potential changes and the modification of the action-potential waveform induced by the problem put the individual in a T. state.
Going back to the potassium channels, Kv7 channels primarily control the interspike interval with a limited effect of the repolarization. Kv3 channels control the repolarization of the action potential and are expected to induce a new state.
The idea is to open the right channels to lead to a neuronal hyperpolarization, thereby stabilizing the membrane potential and decreasing excitability.(No or very little Tinnitus)
Conclusions:
- Despite a drug being potassium channel opener, it has to be very precise to work.
- Flupirtine doesn't act on any sub unit related to T. ( So no possible impact)
- Retigabine acts on interspike interval, meaning less T. spikes and it can possibly repolarize the action potential for some people. But the sub unit range is too wide with numerous side effects. (so it can work to stabilize T. and decrease it to some extent, but is not specific enough to be viable.)
- AUT00063 acts directly on the repolarization and is much more precise, so it's a viable solution providing it works as expected
Thanks for the advice. Tonight I'll take the Trobalt and before going to sleep 1mg of rivotril instead 2mg. I contacted a neurologist experienced enough and told me that the "wash out" the benzo is doable in a week. I'll try. If then goes wrong, I always close at hand.
Ivan and Christian both have had tinnitus longer than Matt, so it's not a big surprise if it takes longer for them to see results. Just hope you do, gents.
Great post on effects, benryu. I still get confused by the different terms, though. Is KV3 one or a family of channels? Is it in the range that retigabine affects or separate?
I was wondering if the effects of retigabine could make someone less likely to respond to AU00063, but from your post, there doesn't seem to be any reason this would happen.
Tomorrow at 1pm EST I'm scheduled to arrive at a new neurologist's office to fill out paperwork ahead of our 1:30 appointment. I mean to ask him for a 3-month prescription, which I can obtain for an $80 co-pay provided I fill it by Thursday midnight. I'm used to pill cutting, so I'll ask for the 300 or 400mg dosage. That way I should be able to dose up 100mg at a time and really stretch the supply.
I'm not totally sure I want to be a guinea pig, but I have to get the pills now or never. If I'm successful, I mean to do more research and consult with the doctor before I take the first pill. If Autifony posts their inclusion criteria for the US trial and it looks like I'll qualify, I may well wait for September. This, of course, I say while my right ear is just barely whistling....
Almost forgot. I had a strange experience of typewriter tinnitus today. I've not had that regularly. It was very distinctive and odd. Since it's not one of my usual noises, I checked my ears for wax and sure enough, they were pretty well plugged. I used my cleaning loop to get them as open as I could and the typing is pretty much gone. Thought I'd post this in case Viking, like me, has been avoiding Q-tips since diagnosis. I think I'll do a coconut oil cleanse tonight and really get the gunk out!
Thank you for this warning. Is there a reason you can explain, please?TROBALT CAN NOT BE CUT OR CRUSHED
@benryu ...Great info post on the K channels!!! Thank you. A little clarification if I may re the below...?
"Going back to the potassium channels, Kv7 channels primarily control the interspike interval with a limited effect of the repolarization. Kv3 channels control the repolarization of the action potential and are expected to induce a new state.
The idea is to open the right channels to lead to a neuronal hyperpolarization, thereby stabilizing the membrane potential and decreasing excitability.(No or very little Tinnitus)"
1. With regard to the "repolarization" of the Kv3 channels. Would another way of saying that be "a re-set"???
Seeing as 'polarization' implies two differing 'polarities', etc. my simple view of it would possibly be that the "T causing event" somehow reversed the polarities at either end off the axon...i.e. the dendrites and the terminal endings at the opposite end. Ummmmmm...Seems like that would be a kind of really 'screwing up event' for a neuron. Ha, ha...which indeed tinnitus seems to be!!!
Anyway, maybe you see my question here? And maybe just Kv3's get "re-set" from whatever they "un-set" into is good enough. [Reminds me of cold re-boot after the old Microsoft 'blue screen of death!' days].
2. How does 'hyperpolarization' (i.e. ramped up/juiced up) supposedly relate to what I was asking above? Sort of like this re-boot or re-set not so much requiring a cold shut down, but a new opened up electric charge kicking it so hard in the arse that it flips polarization back and forth so much that it has no option but to re-set to original configuration...or explode? .
OK, that's it. Sort of above my pay-grade really, but you seem to have a way of saying complex things in English comprehensible for the masses.
P.S. My scrip is in.
Best, Zimichael
Really informative and fascinating post. I hope you are right about these channels. Maybe you should work for Autifony?
Wow - that is quite different to medical research. So does the company you work for now have a video game that involves collecting and crushing life saving pills ;-)Funny story, actually at some point in my life I considered going more on the medical side of research. I have worked a lot with those guys. But I decided to use my data science & research skills in the video game industry. haha
Wow - that is quite different to medical research. So does the company you work for now have a video game that involves collecting and crushing life saving pills ;-)
Maybe we should make one when we find the cure with that being the final level!!!
Do you mean you have worked with the people at Autifony or did you just mean people in the medical field of research in general?I have worked a lot with those guys.
It looks like it can be cut. I'm a little suspicious that they just don't want you to cut it. It's not time released or anything.@Christian78 ...can you please elaborate on this:
TROBALT CAN NOT BE CUT OR CRUSHED
I have managed to get the pharmacy to prescribe 400 mg Potiga and can't seem to get an image of the thing. If it can't be cut into 50 mg sections then I don't want to pay the $$$ for it as I'm not starting on 100 mg TID ( 3 x a day) for sure! I have had some bad experiences with meds and I'm in the 'go real slow' school!
Any chance of a photo of one of your pills???...and sorry what strength are the each again??? You may have said before but this thread is so long already I'm getting lost
Thanks much... Zimichael
Do you mean you have worked with the people at Autifony or did you just mean people in the medical field of research in general?