MemberDon't forget that the university of Pittsburgh are currently working on Retigabine to remove the side effects and suit it for T.. However they only seem to think it will have effect on acute T.
Retigabine (Trobalt, Potiga) — General Discussion
- Thread starter Mpt
- Start date
Don't forget that the university of Pittsburgh are currently working on Retigabine to remove the side effects and suit it for T.. However they only seem to think it will have effect on acute T.
Oh great
How did you find this information?
And the side effects of Retigabine don't sound very good, although Mpt did not mention the walking like a drunk thing.
But: since this is an anti epylepticum, how far can these cause us to get epilepsy later on in our life?
Same thing as ototoxic drugs are use for T treatment, they can cause it too (bad analogy but you get the point).
Is Dr. de Ridder aware of Retigabine?
Oh great
How did you find this information?
Do people even bother to read this thread
*sighIt's litterally on the first page of this thread. Jazz posted a link there and it has been discussed several times througout the thread. Here ya go buddy:
http://www.sciencedaily.com/releases/2013/05/130527153701.htm
Do people even bother to read this thread
It's litterally on the first page of this thread. Jazz posted a link there and it has been discussed several times througout the thread. Here ya go buddy:
http://www.sciencedaily.com/releases/2013/05/130527153701.htm
No, most don't... lol. Although I must admit 58 pages is a bit intimidating.
@Johno Thanks for updating your progress form today. I was especially glad to hear your hissing tinnitus has gone down considerably. That's what my tinnitus is like... a hissing sound. Hopefully similar improvements could be seen for myself as well... sorry if I sound conceited there. I hope that as you go up in the dosage, your tonal tinnitus improves as well buddy.
Johno
Member
- Jan 8, 2014
- 231
- Tinnitus Since
- 6/07/2012
- Cause of Tinnitus
- acoustic trauma
Hudson: Even 50mg entry dosage was relatively effective against hissing. But my tonal T, mainly 1180Hz tone in left is very stable and more intrusive, than other T tones what i have. This eeeeeeee sound is very unpleasant. If it disappears, i will be able to restart my existence
SoulStation
Member
I'd take 1180 Hz over my 3900 Hz. Wanna trade?Hudson: Even 50mg entry dosage was relatively effective against hissing. But my tonal T, mainly 1180Hz tone in left is very stable and more intrusive, than other T tones what i have. This eeeeeeee sound is very unpleasant. If it disappears, i will be able to restart my existence
@Johno I haven't been able to pin my frequency down as closely as you have but I think it's around the 1000Hz range so I know what you're going through. The hissing was my first sign, back when I thought it was my headphones that had the problem, not my Dorsal Cochlear Nucleus. Hope your tone responds to the higher doses.
SteveToHeal
Member
You guys have really low frequency tones (perhaps except the ref to the high eeeeee tone - mine is a high pitch hiss or eeee). Mine is somewhere between 8000 and 8600Hz. As said above, if it would go, i could get my life back.
lcho
Member
- Sep 2, 2014
- 17
- Tinnitus Since
- 06/2014
- Cause of Tinnitus
- Acoustic trauma and prescription-drug induced
I'm currently partaking in the AM-101 trial, I'm about 15 days into it out of 90, however I've had no improvement in either my T or hyperacusis. However I can opt out of the trial whenever I want, and with the Autifony trial coming up, and me currently living in the UK, I'm considering leaving the AM-101 trial and signing up for the Autifony one when it becomes available. Hoping for some input as to whether this would be advisable?
Well, if the vote had gone a different way last week...heh heh.
I'm afraid you're not eligible for Autifony's trial. You need to be 6-18 months into your symptoms. Stick with AM-101 for now and if it's not improved in three months, maybe it'll still be going on. But this could have been discussed on the Autifony thread....
from what I understand retigabine seems to be more efficient than the AM 101 ? I'm a new tinnitus sufferer (not even a month) and I think it already has decreased a bit (not sure if this is psychological though), and i'm definitely considering taking part of the AM 101 trials, but I've seen more post saying that regitabine is efficient than AM 101, what should I do ? Also my tinnitus is noise induced
- Dec 24, 2013
- 933
- Tinnitus Since
- (1956) > 1980 > 2006 > 2012 > (2015)
- Cause of Tinnitus
- Ac. Trauma & Ac.Trauma + Meds.
Hey guys...can we keep this thread on Retigabine please? I'm just coming back into circulation after my "busy-as-hell" week and am doing a lot of bouncing around trying to sift through the backlog. Yeah I know that AUT00063 is integrally linked to Retigabine, and rightly so, but I go there, to that thread to specifically follow up on that, and here to see what the Trobalt/Potiga scoop is. Keeps me more sane... I'm already 
enough!
So a bit of a general update.
First the not so good. Yesterday I woke up with louder ringing and instantly knew it, and at my volume any increase is MOST unwelcome. Plus I was 'aware' of my tinnitus about 100 times more through my day than 'normal'. It was an identical day to the last 5 days. Doing same stuff, same everything. No outside variables the day before either...except the increased Potiga/Trobalt, maybe. I say maybe as I had increased two days before, with evening dose. So I'm not sure if related??? However, Retigabine is the only real variable in my life right now. And yes, I noticed the increase before my first 'morning pill' even.
OK, as you know by now if you have followed my posts over the year I don't do 'short' so for those who want details here is my ramp up schedule to date (numbers = days):
1. 50 mg = total 50 mg
2. 50/50 = total 100 mg
3. 50/50/50 = total 150 mg
4. 50/50/50 = total 150 mg
5. 50/50/75 = total 175 mg
6. 50/50/75 = total 175 mg
7. 75/50/75 = total 200 mg
8. = Today...same as yesterday is the plan, then bump to 75/50/100, or 75/75/75 to = 225 mg tomorrow.
OK, now the good news. This morning my tinnitus is back to 'normal screaming level baseline'..."Bonza!" as they say down under! That is a relief as where do you go from "Level 9"... a "10"??? To me that is the nanosecond of increased T just before the bullet eliminates it forever...So we tend to stay away from Zero and 10.
Ha, ha...even Matt does not say "Zero" for his disappeared T. Superstition lingers in us humanoids and we don't want to tempt those oft' spiteful Gods too much. (Talk to chronic illness patients with weird illnesses, they shy mightily from definitives, as then the egg comes flying to hit them in the face the next day just to mock!)
OK, the rest is for the interested, 'voyeurs' should exit here.
Side effects and future dosage...
I posted in my "User's Update" that I have not been experiencing any fatigue of note yet, and that continues to be the case. However I am still on a low overall dose even though I am ramping up faster than I expected to be. Basically I will continue doing so until I get shit-faced with some side effect I sense I have to back off from. Also as mentioned, initial goal is 100 mg TID (3 x a day) for total of 300 mg per day...which is the 'normal' starting dose.
Then I will hold for a bit. Not sure how long yet, but maybe as long as a week. Minimum 3-5 days. Ultimate goal is 600 mg/day...(Refer back to my 'body weight/plasma levels' posts way back - though will cover in future again if I get there!)
The abdominal pain I mentioned when I jump up in dose...Well, first off, it is not that bad and I can handle it fine. I have had 20 years of practice with this ever since those parasitic predator pukes infected my gut from contaminated domestic water supply in 1993. This current level of "pain" is more like tenderness compared to what I have experienced in the past...often for months on end. This dissipates slowly over the day. Also I was expecting it.
Why?!
Well, those "A" students who have read this thread (or been lucky enough to read it all along instead of coming at it now facing a Godzilla of a task) may recall the 'expected side effects' profile from the research. Here's a refresher for the die hards, c/o the Aussie report (still the bible on Retigabine,...well, except for the few glaring errors):
http://www.tga.gov.au/word/auspar/auspar-retigabine-131017.docx
"KCNQ2, KCNQ3 and KCNQ5 are the dominant forms expressed in neural tissues, but these channels are also expressed in the urinary bladder (all forms, but predominantly KCNQ3), intestine (KCNQ3 in combination with KCNQ1) and skeletal muscles (KCNQ5). KCNQ4 is mainly expressed in the cardiovascular and auditory systems. The expression of these potassium channels in these tissues suggests that retigabine might also cause bladder inhibition, modify gut motility or, most importantly, interfere with cardiac excitability."
So, from the gene expression data, the expected target areas from the development research were those above. See there re. "modify gut motility"?! OK...now you know why I was expecting "issues". Motility screw ups are a common heritage of a prolonged (i.e. 'undiagnosed') Giardia + other microbial scum infection, that gastroenterologists who behaved like a lot of ENTs leave as a legacy. But let's not go there...All to say, the above gave me a hint that I may have gut aspects to watch out for,...as well as keeping a close eye on bladder (that urinary retention) and heart/blood pressure of course.
We cool with that??? Want more explanation of "the few glaring errors"???
OK, so again the "A" students will know what they are...
First up TINNITUS! Yeah, the whole one sentence or whatever, on cochlear/auditory system stuff that was in there. Then came the 'use data' of possibly permanent 'Halloween heavies' = blue lips, blue nails, blue mucosal surfaces, etc. And then the other biggie of potential pigmentation/retinal screw ups in the eyes...These latter ones NOT SO COOL!
So, to end up on all this, it is interesting to note that these latter side effects were not 'expected' in the theoretical and experimental models of the Kv7 channels hit by Retig. (At least from what I can remember). Though there were hints of the hearing stuff and speculation that GSK and Autifony were in on that being down-played. However, I have no interest in digging into that pit again.
I have given quite a bit of thought to numerous aspects of these questions, musings, etc., as my brain was idling in manual labour mode. If there is interest I will continue to post some of those thoughts in future here. [And yeah, Jazz has said this is the thread for that if Retigabine related, which she agrees the Kv channels indeed very much are.]
Ha, ha...there you go. A relatively short post from me compared to what it could have been!
Best, Zimichael
enough!So a bit of a general update.
First the not so good. Yesterday I woke up with louder ringing and instantly knew it, and at my volume any increase is MOST unwelcome. Plus I was 'aware' of my tinnitus about 100 times more through my day than 'normal'. It was an identical day to the last 5 days. Doing same stuff, same everything. No outside variables the day before either...except the increased Potiga/Trobalt, maybe. I say maybe as I had increased two days before, with evening dose. So I'm not sure if related??? However, Retigabine is the only real variable in my life right now. And yes, I noticed the increase before my first 'morning pill' even.
OK, as you know by now if you have followed my posts over the year I don't do 'short' so for those who want details here is my ramp up schedule to date (numbers = days):
1. 50 mg = total 50 mg
2. 50/50 = total 100 mg
3. 50/50/50 = total 150 mg
4. 50/50/50 = total 150 mg
5. 50/50/75 = total 175 mg
6. 50/50/75 = total 175 mg
7. 75/50/75 = total 200 mg
8. = Today...same as yesterday is the plan, then bump to 75/50/100, or 75/75/75 to = 225 mg tomorrow.
OK, now the good news. This morning my tinnitus is back to 'normal screaming level baseline'..."Bonza!" as they say down under! That is a relief as where do you go from "Level 9"... a "10"??? To me that is the nanosecond of increased T just before the bullet eliminates it forever...So we tend to stay away from Zero and 10.
Ha, ha...even Matt does not say "Zero" for his disappeared T. Superstition lingers in us humanoids and we don't want to tempt those oft' spiteful Gods too much. (Talk to chronic illness patients with weird illnesses, they shy mightily from definitives, as then the egg comes flying to hit them in the face the next day just to mock!)
OK, the rest is for the interested, 'voyeurs' should exit here.
Side effects and future dosage...
I posted in my "User's Update" that I have not been experiencing any fatigue of note yet, and that continues to be the case. However I am still on a low overall dose even though I am ramping up faster than I expected to be. Basically I will continue doing so until I get shit-faced with some side effect I sense I have to back off from. Also as mentioned, initial goal is 100 mg TID (3 x a day) for total of 300 mg per day...which is the 'normal' starting dose.
Then I will hold for a bit. Not sure how long yet, but maybe as long as a week. Minimum 3-5 days. Ultimate goal is 600 mg/day...(Refer back to my 'body weight/plasma levels' posts way back - though will cover in future again if I get there!)
The abdominal pain I mentioned when I jump up in dose...Well, first off, it is not that bad and I can handle it fine. I have had 20 years of practice with this ever since those parasitic predator pukes infected my gut from contaminated domestic water supply in 1993. This current level of "pain" is more like tenderness compared to what I have experienced in the past...often for months on end. This dissipates slowly over the day. Also I was expecting it.
Why?!
Well, those "A" students who have read this thread (or been lucky enough to read it all along instead of coming at it now facing a Godzilla of a task) may recall the 'expected side effects' profile from the research. Here's a refresher for the die hards, c/o the Aussie report (still the bible on Retigabine,...well, except for the few glaring errors):
http://www.tga.gov.au/word/auspar/auspar-retigabine-131017.docx
"KCNQ2, KCNQ3 and KCNQ5 are the dominant forms expressed in neural tissues, but these channels are also expressed in the urinary bladder (all forms, but predominantly KCNQ3), intestine (KCNQ3 in combination with KCNQ1) and skeletal muscles (KCNQ5). KCNQ4 is mainly expressed in the cardiovascular and auditory systems. The expression of these potassium channels in these tissues suggests that retigabine might also cause bladder inhibition, modify gut motility or, most importantly, interfere with cardiac excitability."
So, from the gene expression data, the expected target areas from the development research were those above. See there re. "modify gut motility"?! OK...now you know why I was expecting "issues". Motility screw ups are a common heritage of a prolonged (i.e. 'undiagnosed') Giardia + other microbial scum infection, that gastroenterologists who behaved like a lot of ENTs leave as a legacy. But let's not go there...All to say, the above gave me a hint that I may have gut aspects to watch out for,...as well as keeping a close eye on bladder (that urinary retention) and heart/blood pressure of course.
We cool with that??? Want more explanation of "the few glaring errors"???
OK, so again the "A" students will know what they are...
First up TINNITUS! Yeah, the whole one sentence or whatever, on cochlear/auditory system stuff that was in there. Then came the 'use data' of possibly permanent 'Halloween heavies' = blue lips, blue nails, blue mucosal surfaces, etc. And then the other biggie of potential pigmentation/retinal screw ups in the eyes...These latter ones NOT SO COOL!
So, to end up on all this, it is interesting to note that these latter side effects were not 'expected' in the theoretical and experimental models of the Kv7 channels hit by Retig. (At least from what I can remember). Though there were hints of the hearing stuff and speculation that GSK and Autifony were in on that being down-played. However, I have no interest in digging into that pit again.
I have given quite a bit of thought to numerous aspects of these questions, musings, etc., as my brain was idling in manual labour mode. If there is interest I will continue to post some of those thoughts in future here. [And yeah, Jazz has said this is the thread for that if Retigabine related, which she agrees the Kv channels indeed very much are.]
Ha, ha...there you go. A relatively short post from me compared to what it could have been!
Best, Zimichael
- Dec 24, 2013
- 933
- Tinnitus Since
- (1956) > 1980 > 2006 > 2012 > (2015)
- Cause of Tinnitus
- Ac. Trauma & Ac.Trauma + Meds.
Marius...and anyone new to this thread. Before you even THINK about taking this drug...READ THE THREAD!!! Or at least read the numerous side-effects profiles near the very beginning. This stuff is not aspirin. It is highly experimental and IMHO you need to make very informed decision before you pursue it (and good luck getting a prescription even!)
If your tinnitus is very recent, read the Support and Treatments pages first! Use the SEARCH function for your specific idiosyncrasies. There are tons of ideas and options there to mull over before heading for Retigabine. Again, to my mind this is like using an anti-tank weapon where a bow-and-arrow may do just fine.
Good luck...and remember too that most tinnitus suffers (80% plus or minus) adapt completely to their T within 6 months to a year. The effects of Retigabine may be permanent!
Best, Zimichael
Thanks for your advices Zimmichael, i've read a lot in this thread and from what i've understand side-effects are known to appear on high dosage in long time treatment. As you said I'm surely gonna adapt to my tinnitus, actually it's mild so it only bothers me to sleep (not a lot though), but I think that if I can be cured that'd be awesome.
Christian78
Member
- Dec 17, 2013
- 965
- Tinnitus Since
- (Sep 2013)
- Cause of Tinnitus
- progressive tinnitus, time of expiring in next 3-6 months
theekarwash
Member
- Jun 22, 2014
- 158
- Tinnitus Since
- 05/2014
- Cause of Tinnitus
- Noise and/or Ear Infeciton
I've decided I'm going to ask my doctor for retigabine.
Is there any literature you think I should bring to show him? I already have a lot of information already, just wondering if you guys have anything else you think I should bring.
Is there any literature you think I should bring to show him? I already have a lot of information already, just wondering if you guys have anything else you think I should bring.
This article was From 18 months ago. Unfortunately I can't find any recent information. Have you heard any more on their progress?Do people even bother to read this thread
It's litterally on the first page of this thread. Jazz posted a link there and it has been discussed several times througout the thread. Here ya go buddy:
http://www.sciencedaily.com/releases/2013/05/130527153701.htm
@Christian78 Does your latest report mean that you have reduced your other meds to just the sleeping pill?
Because this is on my mind, do you mask at night, Christian? You seem to have problems sleeping and I wondered that was in spite of masking. Just bought a masker for myself today. My chiropractor has one and I get the best rest waiting for her in the adjustment room.
Because this is on my mind, do you mask at night, Christian? You seem to have problems sleeping and I wondered that was in spite of masking. Just bought a masker for myself today. My chiropractor has one and I get the best rest waiting for her in the adjustment room.
- Dec 24, 2013
- 933
- Tinnitus Since
- (1956) > 1980 > 2006 > 2012 > (2015)
- Cause of Tinnitus
- Ac. Trauma & Ac.Trauma + Meds.
Shit!!! Sorry, but no other word seems appropriate.
I have an update to the post I wrote up this morning. The "throw cold water over it" kind...As in 2 + 2 = 4
Four "questionable" things have happened in past day and a bit:
1. As reported, I got the "higher volume tinnitus" day all day Monday...(Which reverted to normal high baseline volume today).
2. This morning I got a phone-call from my son. He does not have a super loud voice. As always I have to use speaker-phone. After about 30 seconds and me turning the volume to lowest setting it was still too loud. I asked him to talk softer. He kinda did, but in a short while I walked to the back of the room and talked from there. It was still a bit loud. (Duh! Michael...you know this one!).
3. I took a celebratory nap this afternoon as my work thing is over. When I woke up an hour later, my ringing volume was up again, like Monday! Sheise! And yes I took my second pill = 50 mg about an hour before.
4. Insurance lady just called - who I have talked to a lot the past few weeks. She does not have loud voice at all. I stood near the phone (on speaker) and was OK sort of, but felt my hearing/ears/whatever-the-hell in there, getting a bit beat up.
OK...my rule is "3 out of 3"...Above is four, though I just pieced the phone thing together after the second call.
Sorry folks, this has happened to me before with very bad results. This is what I call "ototoxic hyperacusis" gearing up. It has happened to me just like this in 2006, and in 2012 a week or so before my fourth increase level of T and H. I did not know what it was in 2006. In 2012 I made the connection too late (as had been on low dose Itraconazole for two weeks during dance performance, but had stopped prior to the 'sound damage event'). So, I am not making the same mistake again.
I can put up with a ton of pain, nausea, brain fog, dizziness, starvation, whatever. But more tinnitus or/or hyperacusis. NO WAY!
So I see two options...
One is to cut back on the Potiga as for sure that is what is doing this. After all, it does affect the auditory system = where "ototoxicity" happens.
Or two...to push it! To take a risk and shine a spotlight on it to make it clearer. That means up my dose and hope to hell it is not a long term screw-up if it goes awol.
At this point I am trending towards "proof", the latter. And very, very much keeping away from any level of sound above gentle voice grade. (My old rule mentioned a lot in early TT Forum posts...."When on heavy duty drugs keep away from loud sound exposure, ototoxic signature or not!"
So tonight's dose I think I will go for 100 mg and see what the hell happens in the morning. Risky, but...to come this far and flame out? Not without a fight.
Incidentally AUT0063 could do the same darn thing. Easily. Just because the Kv7 aspects supposedly affect inter-spike interval does not mean they are not hitting the main T gates as well, otherwise Matt and others would not be getting results. Like I said..."Sheise!"
PS @jazz ...Hey Jazz if you are around could you PM me please?
Zimichael
I have an update to the post I wrote up this morning. The "throw cold water over it" kind...As in 2 + 2 = 4
Four "questionable" things have happened in past day and a bit:
1. As reported, I got the "higher volume tinnitus" day all day Monday...(Which reverted to normal high baseline volume today).
2. This morning I got a phone-call from my son. He does not have a super loud voice. As always I have to use speaker-phone. After about 30 seconds and me turning the volume to lowest setting it was still too loud. I asked him to talk softer. He kinda did, but in a short while I walked to the back of the room and talked from there. It was still a bit loud. (Duh! Michael...you know this one!).
3. I took a celebratory nap this afternoon as my work thing is over. When I woke up an hour later, my ringing volume was up again, like Monday! Sheise! And yes I took my second pill = 50 mg about an hour before.
4. Insurance lady just called - who I have talked to a lot the past few weeks. She does not have loud voice at all. I stood near the phone (on speaker) and was OK sort of, but felt my hearing/ears/whatever-the-hell in there, getting a bit beat up.
OK...my rule is "3 out of 3"...Above is four, though I just pieced the phone thing together after the second call.
Sorry folks, this has happened to me before with very bad results. This is what I call "ototoxic hyperacusis" gearing up. It has happened to me just like this in 2006, and in 2012 a week or so before my fourth increase level of T and H. I did not know what it was in 2006. In 2012 I made the connection too late (as had been on low dose Itraconazole for two weeks during dance performance, but had stopped prior to the 'sound damage event'). So, I am not making the same mistake again.
I can put up with a ton of pain, nausea, brain fog, dizziness, starvation, whatever. But more tinnitus or/or hyperacusis. NO WAY!
So I see two options...
One is to cut back on the Potiga as for sure that is what is doing this. After all, it does affect the auditory system = where "ototoxicity" happens.
Or two...to push it! To take a risk and shine a spotlight on it to make it clearer. That means up my dose and hope to hell it is not a long term screw-up if it goes awol.
At this point I am trending towards "proof", the latter. And very, very much keeping away from any level of sound above gentle voice grade. (My old rule mentioned a lot in early TT Forum posts...."When on heavy duty drugs keep away from loud sound exposure, ototoxic signature or not!"
So tonight's dose I think I will go for 100 mg and see what the hell happens in the morning. Risky, but...to come this far and flame out? Not without a fight.
Incidentally AUT0063 could do the same darn thing. Easily. Just because the Kv7 aspects supposedly affect inter-spike interval does not mean they are not hitting the main T gates as well, otherwise Matt and others would not be getting results. Like I said..."Sheise!"
PS @jazz ...Hey Jazz if you are around could you PM me please?
Zimichael
Some effects are dose dependent. The Retigabine opens your potassium channels at the proper dosage, but perhaps a low dose causes more fluctuation instead of less. Imagine lifting up a heavy garage door. If you put too little strength into it and your hand slips, it's going to slam shut.
You're a brave man to consider moving forward, Michael. I haven't done this research, but it occurs to me that there might be unexpected effects from taking uneven doses. Maybe you're experiencing a plasticity effect where your brain is trying to adapt to the effects of the medication, but because the concentration is unpredictable, your brain is relying too much - or not enough - on the extra permeability induced by the drug. Like a mini withdrawal.
And you're cutting the pills in half to get a 75mg dose, right? I argued in favor of cutting early in the thread, but in light of your experience, maybe we were wrong to doubt the manufacturer. What if instead of 75/75/50 you're really getting 85/63/50? Your brain may be going, "Oh, you're giving me that much help now? Ok, I'll back off on modulating the KCNQ myself then." And then you go into a 16-hour deficit. So your brain expects 85 to be the max, 85*d to be the min, where d is the diminishing effects of time right before your next dose. Let's say the min is 65. That 63mg second dose is already too low, the 50 even more so. Then maybe tomorrow morning's dose is 70.5mg, but it decays to 42mg by the dose #2. See how that could snowball?
Just a theory, but maybe you would do better on a steady dose of 100mg like you suggested. Hang in there!
You're a brave man to consider moving forward, Michael. I haven't done this research, but it occurs to me that there might be unexpected effects from taking uneven doses. Maybe you're experiencing a plasticity effect where your brain is trying to adapt to the effects of the medication, but because the concentration is unpredictable, your brain is relying too much - or not enough - on the extra permeability induced by the drug. Like a mini withdrawal.
And you're cutting the pills in half to get a 75mg dose, right? I argued in favor of cutting early in the thread, but in light of your experience, maybe we were wrong to doubt the manufacturer. What if instead of 75/75/50 you're really getting 85/63/50? Your brain may be going, "Oh, you're giving me that much help now? Ok, I'll back off on modulating the KCNQ myself then." And then you go into a 16-hour deficit. So your brain expects 85 to be the max, 85*d to be the min, where d is the diminishing effects of time right before your next dose. Let's say the min is 65. That 63mg second dose is already too low, the 50 even more so. Then maybe tomorrow morning's dose is 70.5mg, but it decays to 42mg by the dose #2. See how that could snowball?
Just a theory, but maybe you would do better on a steady dose of 100mg like you suggested. Hang in there!
- Dec 24, 2013
- 933
- Tinnitus Since
- (1956) > 1980 > 2006 > 2012 > (2015)
- Cause of Tinnitus
- Ac. Trauma & Ac.Trauma + Meds.
@rtwombly ...hey thanks. Yeah I'm following you, but I don't buy the detail of dose concentration. As you know, the Cmax is reached within a few hours then if 'average Joe or Jane' goes to sleep for 9 or 10 hours after taking pills at supper, then doodlea along to next dose at breakfast...you almost always have messed up plasma levels. Often big time on TID and no midnight dosing. There may be 12 hours between doses with that 'common' sceanario.
For the hell of it here are some ideas I am playing with:
1. I can't imagine the Potiga is eliciting a Glutamate response.
2. I also can't get my mind around a classical "ototoxicity" response...as in frying IHC's or OHC's...or to use Benryu's version...No "Boom!"
3. I also can't see Potiga being like an SSRI and meds that need a few weeks to a month to "build up in the system"...whatever the hell that means, as Cmax is either there or it's not. (Thus with SSRI's it must be a kind of 'learned over weeks plasticity change' going on or...???).
So here, ref Retig. If the locked down Kv channels that are creating the T (no mediation by K+) and not allowing correct repolarization to a 'normal', silent, polarised state in the neuron/cell, (and action potential is thus screwed up royally)...surely it would take a certain dose level to kick that back into shape? Using my old "doors analogy", you need enough force on the door to open it. Just leaning on it with insufficient force goes nowhere, no matter if you do it for weeks. Smash it with a big bulldozer and it opens up...along with God knows what else unless it's Seal Team 6 (aka AUT00063) doing the job with precision.
Thus, I can imagine that if this Retig. crosses the BBB in sufficient concentration IT SHOULD BLOW THE DOORS OPEN WITHOUT ANY DELAY! Either the 'force' is there, or it's not! The tipping point it the tipping point. It requires X amount of force, then it goes.
Thus taking say 500 mg of Potiga at once should give a huge plasma concentration within < 2 hours. Problem is, who knows what else will happen. The usual recommended slow build up is really just to "acclimate" to the side effects IMHO.
4. Another possible idea - "plasticity aspects of Benzos" aside - is to up the Potiga along with a higher dose of Clonazepam to "calm" the reaction or ringing at the same time. Not exactly what I want to do just having Benzo tapered 50-75%, but in theory it could be a plausible strategy. The whole "Benzo good/Benzo bad" argument is a wash re plasticity in my view, as it could work in favour, or against our goal of hitting the T loop and adjusting plasticity thereafter.
Geez, after all this effort I hate to flame out of this test...plus it makes Autifony a lot less 'glorified' FOR ME too, as my "side effect" here is the target...I'm not having urinary retention, or heart crap, or fatigue, etc., etc.
Mulling... Zimichael
For the hell of it here are some ideas I am playing with:
1. I can't imagine the Potiga is eliciting a Glutamate response.
2. I also can't get my mind around a classical "ototoxicity" response...as in frying IHC's or OHC's...or to use Benryu's version...No "Boom!"
3. I also can't see Potiga being like an SSRI and meds that need a few weeks to a month to "build up in the system"...whatever the hell that means, as Cmax is either there or it's not. (Thus with SSRI's it must be a kind of 'learned over weeks plasticity change' going on or...???).
So here, ref Retig. If the locked down Kv channels that are creating the T (no mediation by K+) and not allowing correct repolarization to a 'normal', silent, polarised state in the neuron/cell, (and action potential is thus screwed up royally)...surely it would take a certain dose level to kick that back into shape? Using my old "doors analogy", you need enough force on the door to open it. Just leaning on it with insufficient force goes nowhere, no matter if you do it for weeks. Smash it with a big bulldozer and it opens up...along with God knows what else unless it's Seal Team 6 (aka AUT00063) doing the job with precision.
Thus, I can imagine that if this Retig. crosses the BBB in sufficient concentration IT SHOULD BLOW THE DOORS OPEN WITHOUT ANY DELAY! Either the 'force' is there, or it's not! The tipping point it the tipping point. It requires X amount of force, then it goes.
Thus taking say 500 mg of Potiga at once should give a huge plasma concentration within < 2 hours. Problem is, who knows what else will happen. The usual recommended slow build up is really just to "acclimate" to the side effects IMHO.
4. Another possible idea - "plasticity aspects of Benzos" aside - is to up the Potiga along with a higher dose of Clonazepam to "calm" the reaction or ringing at the same time. Not exactly what I want to do just having Benzo tapered 50-75%, but in theory it could be a plausible strategy. The whole "Benzo good/Benzo bad" argument is a wash re plasticity in my view, as it could work in favour, or against our goal of hitting the T loop and adjusting plasticity thereafter.
Geez, after all this effort I hate to flame out of this test...plus it makes Autifony a lot less 'glorified' FOR ME too, as my "side effect" here is the target...I'm not having urinary retention, or heart crap, or fatigue, etc., etc.
Mulling... Zimichael
@Zimichael, don't compare retigabine to AUT00063. Benryu told us that. If retigabine causes you nothing but grief, you're not less likely to benefit from another drug.
Let's step down from the metaphors for a moment. What retigabine is doing, if I understand correctly (always a big "IF") is lowering the charge at which its target Kv channels are likely to open. So if it's normally -60 that opens 'em wide, now they'll pop at -40. Or whatever. We don't need the detail just now. That makes it more likely for a targeted channel to open, releasing potassium from the cell, changing the polarity inside and outside. It makes the neurons more active than they are in their un-medicated state.
So a low dose may well have an effect. -55 is still easier to achieve than -60. You don't need to bang the door down to peek inside. But maybe, just maybe, nudging the door is only enough to compromise the timing of the cell firing, without actually improving it. Compromised firing could show up as agitation in the your already agitated auditory system. So you and Hengist's spikes could be a positive sign, a sign you're on the right road, and not just a terrible side-effect.
I don't say this to convince you of anything, really. Just theorizing. I agree with you that ototoxicity doesn't seem all that likely, but we don't know enough to rule it out. The Clonazepam thing...if it were me I'd try a higher dose of retigabine for awhile before throwing another drug into the mix, but I get that you're trying to live with the consequences.
Whatever your decision, I hope you'll at least get back to baseline soon. Check the Autifony thread if you haven't seen the new info. I've got an email in to a contact person for the trial.
Let's step down from the metaphors for a moment. What retigabine is doing, if I understand correctly (always a big "IF") is lowering the charge at which its target Kv channels are likely to open. So if it's normally -60 that opens 'em wide, now they'll pop at -40. Or whatever. We don't need the detail just now. That makes it more likely for a targeted channel to open, releasing potassium from the cell, changing the polarity inside and outside. It makes the neurons more active than they are in their un-medicated state.
So a low dose may well have an effect. -55 is still easier to achieve than -60. You don't need to bang the door down to peek inside. But maybe, just maybe, nudging the door is only enough to compromise the timing of the cell firing, without actually improving it. Compromised firing could show up as agitation in the your already agitated auditory system. So you and Hengist's spikes could be a positive sign, a sign you're on the right road, and not just a terrible side-effect.
I don't say this to convince you of anything, really. Just theorizing. I agree with you that ototoxicity doesn't seem all that likely, but we don't know enough to rule it out. The Clonazepam thing...if it were me I'd try a higher dose of retigabine for awhile before throwing another drug into the mix, but I get that you're trying to live with the consequences.
Whatever your decision, I hope you'll at least get back to baseline soon. Check the Autifony thread if you haven't seen the new info. I've got an email in to a contact person for the trial.
Zimichael, sorry to hear about this turn of events. If I may offer my thoughts:
I don't think Potiga is eliciting a glutamate response. In my view, T presents with excited neurons in both the afferent and efferent pathways in the auditory system (afferent is IHC to brain, and efferent is brain to OHC). The efferent pathway modulates the gain on the input, so it could be the case that Potiga is currently working on one pathway more than the other (increasing the gain by repolarizing the afferent neurons more than the effent neurons). This would seem to fit what is happening to you, where what would normally be tolerable volume is being amplified excessively. If one were to take potiga in a sufficient concentration, I would imagine that it would be possible to repolarize all of the aberrant neurons in the entire pathway, and that once this happens T will be eliminated (that's what we are all praying for). So maybe increased concentration would work if this is true (just my views from what I have read, perhaps others can chime in). But it must be a bit scary to have an increase in T at what are already high volume levels, so I would not rule out decreasing, or holding the dosage steady. I seem to recall reading that it is in the increases of dosage with this drug that the side effects are most frequently experienced. Also, I think @Christian78 had some issues similar what you are describing (a great regression followed by improvement), so maybe his input would help. I think avoiding noises during this sensitive part of the dosage intake might be helpful. In my opinion you should hold the clonazepam steady so that you can at least control that variable.
- Dec 24, 2013
- 933
- Tinnitus Since
- (1956) > 1980 > 2006 > 2012 > (2015)
- Cause of Tinnitus
- Ac. Trauma & Ac.Trauma + Meds.
Hey rt @rtwombly and loco' @locoyeti ...thanks much for great feedback! Yeah we are all on the same page here. I understand what you guys are saying and from my last post was mulling those nuances. I just saw the Autifony info too and it made 100% sense that they are using a "big kick" of one 800 mg dose per day...not a TID or QID thing. So the steady-state plasma levels get a bit questionable unless they have "timed-release" going with their pills. Of course we don't know exactly what the pharmacokinetics are but sure looks like the "Blam!" approach...daily. With a fine tuned methodology just hitting Kv3, it may be a lot easier and safer to do than with the "Gang of Four" that Retig. is hitting. Too many side effect weirdness profiles in that/this mish mash!
Loco'...Yeah, it's hard to know what may be happening with afferent and efferent balance once T and H has set in, but they seem to be acting in concert for me right now...But not consistently. I can't really evaluate the H without a stimulus (phone conversation say), but the T volume is being weird, especially if it were plasma concentration related...Like why all day Monday, then not today until a nap, but same doses??? (And I'm good at cutting pills = not that far off). And slowly T volume has gone to baseline again this evening. Thus maybe anomalies with membrane potentials, etc., etc.
Gawd knows...but I'm doing the jump up to 100 mg TID with 8 hour intervals. Took first as of 9:00 pm tonight. Next 100 mg pill at 5:00 am unless ears are screaming too freakily. Then next at 1:00 pm...then evaluate. (So much for the taper plan!)...And FOR SURE, no sound exposure of note...That's my rule number one in case like this. Par for the course.
OK, will see what tomorrow brings...And thanks again! Nice to see familiar voices that have been through all this Retig from way back too. (Also need to check on Hengist! Got side-tracked by my own version).
Best, Zimichael
Loco'...Yeah, it's hard to know what may be happening with afferent and efferent balance once T and H has set in, but they seem to be acting in concert for me right now...But not consistently. I can't really evaluate the H without a stimulus (phone conversation say), but the T volume is being weird, especially if it were plasma concentration related...Like why all day Monday, then not today until a nap, but same doses??? (And I'm good at cutting pills = not that far off). And slowly T volume has gone to baseline again this evening. Thus maybe anomalies with membrane potentials, etc., etc.
Gawd knows...but I'm doing the jump up to 100 mg TID with 8 hour intervals. Took first as of 9:00 pm tonight. Next 100 mg pill at 5:00 am unless ears are screaming too freakily. Then next at 1:00 pm...then evaluate. (So much for the taper plan!)...And FOR SURE, no sound exposure of note...That's my rule number one in case like this. Par for the course.
OK, will see what tomorrow brings...And thanks again! Nice to see familiar voices that have been through all this Retig from way back too. (Also need to check on Hengist! Got side-tracked by my own version).
Best, Zimichael
undecided
Member
@Zimichael you've had tinnitus for a long time.
I guess that it would take quite a big (lengthy) commitment on your part to repair "damage" that has been in progress for such a long time. My 2 cents anyway.
It's not my place to offer any advice concerning your health, if I were in your shoes I wouldn't know if it would be wise to continue.
But you have my respect and appreciation for hanging in there.
I guess that it would take quite a big (lengthy) commitment on your part to repair "damage" that has been in progress for such a long time. My 2 cents anyway.
It's not my place to offer any advice concerning your health, if I were in your shoes I wouldn't know if it would be wise to continue.
But you have my respect and appreciation for hanging in there.
- Dec 24, 2013
- 933
- Tinnitus Since
- (1956) > 1980 > 2006 > 2012 > (2015)
- Cause of Tinnitus
- Ac. Trauma & Ac.Trauma + Meds.
Woke up this morning with 'normal baseline' (9) ringing. Took another 100 mg of Potiga exactly at 5:00 am, 8 hours after taking 100 mg at 9:00 pm last night. No idea about H aspect yet as no phone-calls at this hour (or caller gets eviscerated in no uncertain terms!).
Well so much for 'fluctuating plasma levels' holding to any sort of linear function with precision, as mine must have been going all over the place by now. Midday dose yesterday was 50 mg (was doing 75/50/75), so was already 'decaying downward' so to speak pretty good by 9:00 pm! With a Retig. half life of supposedly 8-10 hours and the higher 75 mg early morning, there was a significant cumulative 'decay' effect as @rtwombly correctly pointed out. So my viewpoint on this aspect is still up for grabs. However, to placate the "Meds Gods" I am doing exact 8 hour dosing intervals...for the present. [See later].
OK, now I realize a lot of this stuff can get pretty technical. I also realize that all of us here (as far as I know, and @benryu aside) are not professional geneticists or neurologists...IF YOU ARE CAN YOU PLEASE STEP UP AND SAY SO...seriously! I would sure like to know. As I, along with the other testers/trialees we are taking some risks here and professional input would be appreciated.
For those who are following this thread and are getting lost, or bored, or frustrated with this "technical stuff" (and the length of my posts
)...I'm sorry, but to be blunt, this is exactly what we should be doing! Picking this stuff apart and looking at it in as many ways as possible, stumbling and bumbling along through intricate neurology as we go. I think we are doing a stellar job and I have great respect for our "group mind" process and the input of trialees to date. And if you think this is too theoretical and speculative, let me very clearly say...If I/we had not done the homework on this drug there is no way in hell I would be doing anything but tapering fast as of yesterday afternoon!!! After what I have been through (see my recently updated 'Profile' if need to), no iota of a doubt.
*[For those who know the details = the very high probability of no Glutamate cascade - foremost, and the polarity functions we have thrashed though, swayed my decision to continue].
End of speech!...And yeah, this may be a long post, as just starting proper.
Now for some meat, and hopefully some detailed brainstorming by those dedicated to this aspect, plus some fine tuned questions later for current or past trialees.
Even before I found out about the Autifony Trial Details post (kinda scummy huh!) I had been writing to jazz about how it did not make sense to me re dose function. I pasted that a bit later on this thread ref. "kicking the door open" etc. with a big one time dose, as either the K gate was open or closed. Yeah, maybe it gets pushed open a wee bit as rt suggested, but with electrical activity to my simple mind, it tends to be "on" or "off"....Mmmm, unless there's a short, but then there's a real fry up!
Anyhow, when I woke up this morning I had this much clearer realization that basically we are dosing Retigabine here in our TT trial, as per epilepsy!!! (And the "Matt Model", which is also the epilepsy model as per GSK recommenced dosages and frequencies thereof).
Why are we doing that??? Because we are exploring and figuring it out, so best to stay with the recommendations! OK, think about it...Again, I may just be a mumbling mothball here, but would it not make perfect sense to keep a steady plasma and trans BBB (blood brain barrier) level for something like epilepsy? Where jagged spiking needs a constant clampdown to keep it under control and contained? The idea is "prevention" right? Steady concentration sounds good to me for that!
But tinnitus...Simply speaking, (and if we go with Autifony focusing for a specific reason on just one channel!) the KV3 gate is stuck shut and needs to be opened to allow more K+ ions through to normalize the polarity, etc. Now going off memory here (and really, I had not even thought about an axon in 40 years c/o Psych II class in 1972 until this thread...and what we are talking about here is light years ahead of that age!) so apologies if I have this arse about face...OK, the core aspect of the model is to get the Kv channel working again, then hopefully over time revert to a: "Hey cool, we remember this state, let's keep it this way!" = a plasticity 'remodel' of the auditory network, etc., etc. [Hey @benryu when are you getting off that beach!!!???].
Now doesn't it make more sense to do a big kick at the door than a steady push??? If this idea has merit, then there would be an open/closed tipping point where the K+ ions are just loading up too heavy and they finally burst through. Aka the 800 mg, one dose AUT00063. Then the gate is open and repolarization can take place, etc.
Yeah I may be talking rocks here but please shoot this down. Open invite!!!
Now there are all sorts of problems with this approach c/o Retigabine/Trobalt/Potiga.
One is that Retig. is not even supposedly hitting Kv3 pathways...(and Autifony is there for a reason! Oh, and by the way the "spin-off of GSK" in the Autifony trial details puts that little marriage hypothesis to rest!). Yet obviously Retig. is or we would not be getting T results with it. At minimum there is 'bleed off' to some aspects of T function.
However, the Kv7 "Gang of Four" (KCNQ 2-5, or Kv7.2-7.5) are also obviously hitting "other brain areas" or we would not be having "side effects" like urinary retention; potential heart issues; Halloween highlights on nails, lips, mucosal surfaces; and then retinal pigmentation issues; etc. There has to be brain aspects for that stuff to happen.
Thus upping to a one time bulldozer dose of Retigabine is much more risky that using a precision guided bullet like AUT00063. Problema no???!!!
Any volunteers want to test this out??? Hey, look at the bright side, overall DAILY dose may be less than 900 mg. Just one BIG dose. Maybe 400 mg would do it? Maybe 500 mg?...But maybe not either.
Speaking of which...COULD OUR CURRENT TESTERS/TRIALEES PLEASE CHECK IN HERE ON THE THREAD! I have some very nuanced questions I would very much appreciate answers to if possible...However, I only know for sure that @Christian78, @Johno, @SoulStation (are you still with us?), @Bogdan, and @Mpt (tapering right?) are active. Sorry if I left someone out. *[List on page one is out of date]. And @Hengist are you OK???!!!
So for you testers, so far...a very detail oriented question if I may. (And I already half know the answer = "variable!"):
Have you/did you notice, when your tinnitus was first affected, if there was a certain dose level that suddenly affected it...or was it slow progression, getting more and more 'affected' in a linear (dose related) fashion?
Now I realize this could be tough to answer, but any light on this would be most helpful, even if that light shows absolutely zero connection or similarity with/to each of you.
OK...I should quit here, as this is way enough data, questions, etc. for one post...and I'm getting hungry. Three hours on this already. Phew! [Throw this bum off the board he is an unbearable old fart chewing up bandwidth!!! Ha, ha.]
Oh and food...No gut pain so far with current dose increases, so may just be my old gut-and-me fight that was doing it, as generally have to take meds with food. This 5:00 am dose was not! Fingers crossed...
And yeah, I do have more questions!!!
Later. Best, Zimichael
Well so much for 'fluctuating plasma levels' holding to any sort of linear function with precision, as mine must have been going all over the place by now. Midday dose yesterday was 50 mg (was doing 75/50/75), so was already 'decaying downward' so to speak pretty good by 9:00 pm! With a Retig. half life of supposedly 8-10 hours and the higher 75 mg early morning, there was a significant cumulative 'decay' effect as @rtwombly correctly pointed out. So my viewpoint on this aspect is still up for grabs. However, to placate the "Meds Gods" I am doing exact 8 hour dosing intervals...for the present. [See later].
OK, now I realize a lot of this stuff can get pretty technical. I also realize that all of us here (as far as I know, and @benryu aside) are not professional geneticists or neurologists...IF YOU ARE CAN YOU PLEASE STEP UP AND SAY SO...seriously! I would sure like to know. As I, along with the other testers/trialees we are taking some risks here and professional input would be appreciated.
For those who are following this thread and are getting lost, or bored, or frustrated with this "technical stuff" (and the length of my posts
)...I'm sorry, but to be blunt, this is exactly what we should be doing! Picking this stuff apart and looking at it in as many ways as possible, stumbling and bumbling along through intricate neurology as we go. I think we are doing a stellar job and I have great respect for our "group mind" process and the input of trialees to date. And if you think this is too theoretical and speculative, let me very clearly say...If I/we had not done the homework on this drug there is no way in hell I would be doing anything but tapering fast as of yesterday afternoon!!! After what I have been through (see my recently updated 'Profile' if need to), no iota of a doubt.*[For those who know the details = the very high probability of no Glutamate cascade - foremost, and the polarity functions we have thrashed though, swayed my decision to continue].
End of speech!...And yeah, this may be a long post, as just starting proper.
Now for some meat, and hopefully some detailed brainstorming by those dedicated to this aspect, plus some fine tuned questions later for current or past trialees.
Even before I found out about the Autifony Trial Details post (kinda scummy huh!) I had been writing to jazz about how it did not make sense to me re dose function. I pasted that a bit later on this thread ref. "kicking the door open" etc. with a big one time dose, as either the K gate was open or closed. Yeah, maybe it gets pushed open a wee bit as rt suggested, but with electrical activity to my simple mind, it tends to be "on" or "off"....Mmmm, unless there's a short, but then there's a real fry up!
Anyhow, when I woke up this morning I had this much clearer realization that basically we are dosing Retigabine here in our TT trial, as per epilepsy!!! (And the "Matt Model", which is also the epilepsy model as per GSK recommenced dosages and frequencies thereof).
Why are we doing that??? Because we are exploring and figuring it out, so best to stay with the recommendations! OK, think about it...Again, I may just be a mumbling mothball here, but would it not make perfect sense to keep a steady plasma and trans BBB (blood brain barrier) level for something like epilepsy? Where jagged spiking needs a constant clampdown to keep it under control and contained? The idea is "prevention" right? Steady concentration sounds good to me for that!
But tinnitus...Simply speaking, (and if we go with Autifony focusing for a specific reason on just one channel!) the KV3 gate is stuck shut and needs to be opened to allow more K+ ions through to normalize the polarity, etc. Now going off memory here (and really, I had not even thought about an axon in 40 years c/o Psych II class in 1972 until this thread...and what we are talking about here is light years ahead of that age!) so apologies if I have this arse about face...OK, the core aspect of the model is to get the Kv channel working again, then hopefully over time revert to a: "Hey cool, we remember this state, let's keep it this way!" = a plasticity 'remodel' of the auditory network, etc., etc. [Hey @benryu when are you getting off that beach!!!???].
Now doesn't it make more sense to do a big kick at the door than a steady push??? If this idea has merit, then there would be an open/closed tipping point where the K+ ions are just loading up too heavy and they finally burst through. Aka the 800 mg, one dose AUT00063. Then the gate is open and repolarization can take place, etc.
Yeah I may be talking rocks here but please shoot this down. Open invite!!!
Now there are all sorts of problems with this approach c/o Retigabine/Trobalt/Potiga.
One is that Retig. is not even supposedly hitting Kv3 pathways...(and Autifony is there for a reason! Oh, and by the way the "spin-off of GSK" in the Autifony trial details puts that little marriage hypothesis to rest!). Yet obviously Retig. is or we would not be getting T results with it. At minimum there is 'bleed off' to some aspects of T function.
However, the Kv7 "Gang of Four" (KCNQ 2-5, or Kv7.2-7.5) are also obviously hitting "other brain areas" or we would not be having "side effects" like urinary retention; potential heart issues; Halloween highlights on nails, lips, mucosal surfaces; and then retinal pigmentation issues; etc. There has to be brain aspects for that stuff to happen.
Thus upping to a one time bulldozer dose of Retigabine is much more risky that using a precision guided bullet like AUT00063. Problema no???!!!
Any volunteers want to test this out??? Hey, look at the bright side, overall DAILY dose may be less than 900 mg. Just one BIG dose. Maybe 400 mg would do it? Maybe 500 mg?...But maybe not either.
Speaking of which...COULD OUR CURRENT TESTERS/TRIALEES PLEASE CHECK IN HERE ON THE THREAD! I have some very nuanced questions I would very much appreciate answers to if possible...However, I only know for sure that @Christian78, @Johno, @SoulStation (are you still with us?), @Bogdan, and @Mpt (tapering right?) are active. Sorry if I left someone out. *[List on page one is out of date]. And @Hengist are you OK???!!!
So for you testers, so far...a very detail oriented question if I may. (And I already half know the answer = "variable!"):
Have you/did you notice, when your tinnitus was first affected, if there was a certain dose level that suddenly affected it...or was it slow progression, getting more and more 'affected' in a linear (dose related) fashion?
Now I realize this could be tough to answer, but any light on this would be most helpful, even if that light shows absolutely zero connection or similarity with/to each of you.
OK...I should quit here, as this is way enough data, questions, etc. for one post...and I'm getting hungry. Three hours on this already. Phew! [Throw this bum off the board he is an unbearable old fart chewing up bandwidth!!! Ha, ha.]
Oh and food...No gut pain so far with current dose increases, so may just be my old gut-and-me fight that was doing it, as generally have to take meds with food. This 5:00 am dose was not! Fingers crossed...
And yeah, I do have more questions!!!
Later. Best, Zimichael
Woke up this morning with 'normal baseline' (9) ringing. Took another 100 mg of Potiga exactly at 5:00 am, 8 hours after taking 100 mg at 9:00 pm last night. No idea about H aspect yet as no phone-calls at this hour (or caller gets eviscerated in no uncertain terms!).
Well so much for 'fluctuating plasma levels' holding to any sort of linear function with precision, as mine must have been going all over the place by now. Midday dose yesterday was 50 mg (was doing 75/50/75), so was already 'decaying downward' so to speak pretty good by 9:00 pm! With a Retig. half life of supposedly 8-10 hours and the higher 75 mg early morning, there was a significant cumulative 'decay' effect as @rtwombly correctly pointed out. So my viewpoint on this aspect is still up for grabs. However, to placate the "Meds Gods" I am doing exact 8 hour dosing intervals...for the present. [See later].
OK, now I realize a lot of this stuff can get pretty technical. I also realize that all of us here (as far as I know, and @benryu aside) are not professional geneticists or neurologists...IF YOU ARE CAN YOU PLEASE STEP UP AND SAY SO...seriously! I would sure like to know. As I, along with the other testers/trialees we are taking some risks here and professional input would be appreciated.
For those who are following this thread and are getting lost, or bored, or frustrated with this "technical stuff" (and the length of my posts
*[For those who know the details = the very high probability of no Glutamate cascade - foremost, and the polarity functions we have thrashed though, swayed my decision to continue].
End of speech!...And yeah, this may be a long post, as just starting proper.
Now for some meat, and hopefully some detailed brainstorming by those dedicated to this aspect, plus some fine tuned questions later for current or past trialees.
Even before I found out about the Autifony Trial Details post (kinda scummy huh!) I had been writing to jazz about how it did not make sense to me re dose function. I pasted that a bit later on this thread ref. "kicking the door open" etc. with a big one time dose, as either the K gate was open or closed. Yeah, maybe it gets pushed open a wee bit as rt suggested, but with electrical activity to my simple mind, it tends to be "on" or "off"....Mmmm, unless there's a short, but then there's a real fry up!
Anyhow, when I woke up this morning I had this much clearer realization that basically we are dosing Retigabine here in our TT trial, as per epilepsy!!! (And the "Matt Model", which is also the epilepsy model as per GSK recommenced dosages and frequencies thereof).
Why are we doing that??? Because we are exploring and figuring it out, so best to stay with the recommendations! OK, think about it...Again, I may just be a mumbling mothball here, but would it not make perfect sense to keep a steady plasma and trans BBB (blood brain barrier) level for something like epilepsy? Where jagged spiking needs a constant clampdown to keep it under control and contained? The idea is "prevention" right? Steady concentration sounds good to me for that!
But tinnitus...Simply speaking, (and if we go with Autifony focusing for a specific reason on just one channel!) the KV3 gate is stuck shut and needs to be opened to allow more K+ ions through to normalize the polarity, etc. Now going off memory here (and really, I had not even thought about an axon in 40 years c/o Psych II class in 1972 until this thread...and what we are talking about here is light years ahead of that age!) so apologies if I have this arse about face...OK, the core aspect of the model is to get the Kv channel working again, then hopefully over time revert to a: "Hey cool, we remember this state, let's keep it this way!" = a plasticity 'remodel' of the auditory network, etc., etc. [Hey @benryu when are you getting off that beach!!!???].
Now doesn't it make more sense to do a big kick at the door than a steady push??? If this idea has merit, then there would be an open/closed tipping point where the K+ ions are just loading up too heavy and they finally burst through. Aka the 800 mg, one dose AUT00063. Then the gate is open and repolarization can take place, etc.
Yeah I may be talking rocks here but please shoot this down. Open invite!!!
Now there are all sorts of problems with this approach c/o Retigabine/Trobalt/Potiga.
One is that Retig. is not even supposedly hitting Kv3 pathways...(and Autifony is there for a reason! Oh, and by the way the "spin-off of GSK" in the Autifony trial details puts that little marriage hypothesis to rest!). Yet obviously Retig. is or we would not be getting T results with it. At minimum there is 'bleed off' to some aspects of T function.
However, the Kv7 "Gang of Four" (KCNQ 2-5, or Kv7.2-7.5) are also obviously hitting "other brain areas" or we would not be having "side effects" like urinary retention; potential heart issues; Halloween highlights on nails, lips, mucosal surfaces; and then retinal pigmentation issues; etc. There has to be brain aspects for that stuff to happen.
Thus upping to a one time bulldozer dose of Retigabine is much more risky that using a precision guided bullet like AUT00063. Problema no???!!!
Any volunteers want to test this out??? Hey, look at the bright side, overall DAILY dose may be less than 900 mg. Just one BIG dose. Maybe 400 mg would do it? Maybe 500 mg?...But maybe not either.
Speaking of which...COULD OUR CURRENT TESTERS/TRIALEES PLEASE CHECK IN HERE ON THE THREAD! I have some very nuanced questions I would very much appreciate answers to if possible...However, I only know for sure that @Christian78, @Johno, @SoulStation (are you still with us?), @Bogdan, and @Mpt (tapering right?) are active. Sorry if I left someone out. *[List on page one is out of date]. And @Hengist are you OK???!!!
So for you testers, so far...a very detail oriented question if I may. (And I already half know the answer = "variable!"):
Have you/did you notice, when your tinnitus was first affected, if there was a certain dose level that suddenly affected it...or was it slow progression, getting more and more 'affected' in a linear (dose related) fashion?
Now I realize this could be tough to answer, but any light on this would be most helpful, even if that light shows absolutely zero connection or similarity with/to each of you.
OK...I should quit here, as this is way enough data, questions, etc. for one post...and I'm getting hungry. Three hours on this already. Phew! [Throw this bum off the board he is an unbearable old fart chewing up bandwidth!!! Ha, ha.]
Oh and food...No gut pain so far with current dose increases, so may just be my old gut-and-me fight that was doing it, as generally have to take meds with food. This 5:00 am dose was not! Fingers crossed...
And yeah, I do have more questions!!!
Later. Best, Zimichael
@Zimichael Maybe I didn't catch it in there. How's your tinnitus today? Is it doing better?
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