need to remember though that Christian is taking other medications as well at the same time. If we have someone taking trobalt alone on here at present, with no other meds at the same time, it would be interesting to see what, if any, side effects they have compared to others, as we all know how meds can interact and cause side effects to seem / be worse.
Retigabine (Trobalt, Potiga) — General Discussion
- Thread starter Mpt
- Start date
need to remember though that Christian is taking other medications as well at the same time. If we have someone taking trobalt alone on here at present, with no other meds at the same time, it would be interesting to see what, if any, side effects they have compared to others, as we all know how meds can interact and cause side effects to seem / be worse.
Member
Christian78
Member
- Dec 17, 2013
- 965
- Tinnitus Since
- (Sep 2013)
- Cause of Tinnitus
- progressive tinnitus, time of expiring in next 3-6 months
I wondered how this Troblat stuff worked, and i came across the below explanation. This document was written by 3 Glaxo SK staff members, and one was a certain Mr Large, who we all know now of course. He obviously saw the connection whilst working on Trobalt for sure and has put that knowledge into aut063,
Article
The mechanism of action of retigabine (ezogabine), a first-in-class K+ channel opener for the treatment of epilepsy.
New Frontiers Science Park, GlaxoSmithKline plc, Harlow, Essex, United Kingdom
Martin J Gunthorpe Charles H Large Raman Sankar
KCNQ channels are active at the normal cell resting membrane potential (RMP) and contribute a continual hyperpolarizing influence that stabilizes cellular excitability. The Mechanism of action of Retagabine increases the number of KCNQ channels that are open at rest and also primes the cell to retort with a larger, more rapid, and more prolonged response to membrane depolarization or increased neuronal excitability. In this way, Retagabine amplifies this natural inhibitory force in the brain, acting like a brake to prevent the high levels of neuronal action potential burst firing that may accompany sustained depolarizations associated with the initiation and propagation of seizures.
Article
The mechanism of action of retigabine (ezogabine), a first-in-class K+ channel opener for the treatment of epilepsy.
New Frontiers Science Park, GlaxoSmithKline plc, Harlow, Essex, United Kingdom
Martin J Gunthorpe Charles H Large Raman Sankar
KCNQ channels are active at the normal cell resting membrane potential (RMP) and contribute a continual hyperpolarizing influence that stabilizes cellular excitability. The Mechanism of action of Retagabine increases the number of KCNQ channels that are open at rest and also primes the cell to retort with a larger, more rapid, and more prolonged response to membrane depolarization or increased neuronal excitability. In this way, Retagabine amplifies this natural inhibitory force in the brain, acting like a brake to prevent the high levels of neuronal action potential burst firing that may accompany sustained depolarizations associated with the initiation and propagation of seizures.
- Dec 24, 2013
- 933
- Tinnitus Since
- (1956) > 1980 > 2006 > 2012 > (2015)
- Cause of Tinnitus
- Ac. Trauma & Ac.Trauma + Meds.
Eric... Have been reading your posts here and may I make a gentle suggestion that you try and stick to "Retigabine" as the primary aspect of any responses...as this thread is becoming a HUGE monster of a thing and back-navigating to find things is 'challenging' for oldies (I mean 'age' there
) like me.Also, if you look around on the main Support page (or history/search), plus some other sections, you will find tons of stuff that relate more to your issues and situation (short term/recent tinnitus) which could prove more helpful than this pretty risky, wild card 'experiment' we are doing here...You do NOT want to just go taking Retigabine without being very well informed IMHO. To me it's more of a last resort thing, and you have only had T for a few months...You may well be one of the vast majority who adapt to it and live with it just fine. Honest, it's the norm, not the exception. Some probing on this site will show you just that.
Lastly, to re-emphasize...Yes, by all means keep tabs on this thread, but I would be heavily zeroing in on 'recent tinnitus' help strategies, TMJ posts, etc., etc., not the heavy duty 'got this forever' aspects.
Good luck... Best, Zimichael
- Dec 24, 2013
- 933
- Tinnitus Since
- (1956) > 1980 > 2006 > 2012 > (2015)
- Cause of Tinnitus
- Ac. Trauma & Ac.Trauma + Meds.
Hey @111 ...I'm pretty darn sure this was posted way back on this thread as I sure read it (and there were numerous speculative ideas about Charles Large, and his Retig. research flowing over to Autifony, GSK, etc., etc.), but of course I can't find it because this thread is so small and short! Being sarcastic of course
. Hell it may have even been on the Autifony thread (the incestuous twin of this one)...but both de rigeur to read (ahhh...wade through) at regular intervals.Anyway, for those who missed it, your post/article ref. can enlighten, but also do go back to see we already thrashed this horse into the mud.
Best, Zimichael
Very quite here.
Any news from the Retigabine patients?
What I am wondering is if I should try Retigabine or wait for AUT000063.
If AUT is available only 2018 or 2019 (if at all) for the public, this would be a very long time.
Any news from the Retigabine patients?
What I am wondering is if I should try Retigabine or wait for AUT000063.
If AUT is available only 2018 or 2019 (if at all) for the public, this would be a very long time.
Yes. Member ATEOS mentioned already that they also gave AUT to some T patients in phase I.@Martin69
Maybe wait a bit longer to see how the AUT trials will go, if not good then we have no choice but go for retigabine!
Let's hope we get more positive news from members who are currently on it
Maybe we know sooner than we expect if this will help or not.
I hope so. Still difficult handling the dog whistle in my head.
wonder if anyone would like to see if these can supply trobalt direct to them, dont think they would require a prescription ?
www.merrychemical.com/sell-offer_retigabine_cas_no_150812_12_7-84312.html
www.merrychemical.com/sell-offer_retigabine_cas_no_150812_12_7-84312.html
SteveToHeal
Member
let's not be over-suspicious of the Chinese, they make almost everything we have.
If its a real lab they can do the job no problem,and they will be looking to please because
they want repeat business.
a shame you cant get it from your doc, as its also been indicated for anxiety!
i might be wrong but i think i saw that somewhere.
here you are:
Anxiolytic effects of Maxipost (BMS-204352) and retigabine via activation of neuronal Kv7 channels.
http://www.ncbi.nlm.nih.gov/pubmed/15814569
http://medind.nic.in/ibi/t05/i5/ibit05i5p340.pdf (retigabine: a novel anticonvulsant)
As compared to other antiepileptic agents, retigabine is
unique in that it selectively activates potassium ion channels Kv 7.2-Kv7.5 and not cardiac Kv 7.1, thereby avoiding cardiac side effects.
Clinical data obtained thus far indicate that retigabine is well tolerated in humans when titrated up to its
therapeutic dose range. No tolerance, drug dependence, or withdrawal liability has been reported
maybe the anxiolytic effects of retigabine give it a double advantage.
looking at the results so far, and these good people are telling us
how it is (probably more trustworthy than a clinical trial!),
retigabine is WORKING.
i mean, if the autifony trial reports back this kind of result, everyone will say its the real deal.
but why is retigabine working so well if the channels are
so specific, is it a back door mechanism, im sure this
has already been explained in the thread, but anyone care to comment.
looking at the results so far, and these good people are telling us
how it is (probably more trustworthy than a clinical trial!),
retigabine is WORKING.
i mean, if the autifony trial reports back this kind of result, everyone will say its the real deal.
but why is retigabine working so well if the channels are
so specific, is it a back door mechanism, im sure this
has already been explained in the thread, but anyone care to comment.
lol got a email back from AM-101 saying Unfortunately, ototoxicity induced tinnitus does not qualify to participate in this study. I hope you find relief from your tinnitus. guess ill have to wait for AUT00063
Christian78
Member
- Dec 17, 2013
- 965
- Tinnitus Since
- (Sep 2013)
- Cause of Tinnitus
- progressive tinnitus, time of expiring in next 3-6 months
I read your posts people. I am using retigabine 200 mg now bit more than one month, i will not say i feel t free but it helps, sometimes hugely other times less, but still it is helping it from hurting me. and yes it keeping me from hurting myself and thinking about suicide. Yes i can leave house, I just live alone so it is a big problem. Next big problem is it that I need to learn thing and study and retigabine makes me zombie, at least 1--2h, sometimes even full 8 h after taking pill, it is amnesia making a problem.
But when I see you, written you will wait for Aut00063 congratulation. I am sure your t is small, because it was significant you look for retigabine to survive until Autifony if the Aut ever comes out. So I must say I lough when people say they wait for autifony. It was supposed to start end of summer, now September, October, then it will last 2a phase, then will come 2b phase, then they will take 6 months to write report. You are speaking you will wait 1,2 y to see is there is something from autifony!!! and it is just phase. Dont hope you will get in, chance is 0.01%. And if you do what. Autifopny is not permanent cure, you would have to take it. and again one can use retigabine and stop and start autifony.
But when I see you, written you will wait for Aut00063 congratulation. I am sure your t is small, because it was significant you look for retigabine to survive until Autifony if the Aut ever comes out. So I must say I lough when people say they wait for autifony. It was supposed to start end of summer, now September, October, then it will last 2a phase, then will come 2b phase, then they will take 6 months to write report. You are speaking you will wait 1,2 y to see is there is something from autifony!!! and it is just phase. Dont hope you will get in, chance is 0.01%. And if you do what. Autifopny is not permanent cure, you would have to take it. and again one can use retigabine and stop and start autifony.
Christian78
Member
- Dec 17, 2013
- 965
- Tinnitus Since
- (Sep 2013)
- Cause of Tinnitus
- progressive tinnitus, time of expiring in next 3-6 months
- Dec 24, 2013
- 933
- Tinnitus Since
- (1956) > 1980 > 2006 > 2012 > (2015)
- Cause of Tinnitus
- Ac. Trauma & Ac.Trauma + Meds.
Hey @william2 ...(Sigh! Nothing on your "Profile" page except that you joined Thursday)
Good find on this, and as usual it is going to take some time to sort through. Anyone else digging here????
A few points in case before we start jumping to new/more conclusions:
The second paper (medind...) is dated October 2005. As we know the "blue lips and Wolverine eyes" thing was not even on the radar in 2011 and was a 'non-mention' in the Retig. definitive document c/o Australian Public Assessment Report in 2013. So there is "time/date" thing here to be wary of.
Also this therein...Shiese!!! It won't cut and paste!!! Well here is few lines of me manually typing:
"In addition to acting on potassium ion channels, retigabine also affects GABA neurotransmission in the GABA receptor, which is a key inhibitory receptor in the central nervous system and is implicated in epilepsy. Malfunctioning of the GABA receptor leads to hyperexcitability in the brain, which causes seizures, making this receptor an important target for antiepileptic therapeutics. Apart from increasing the concentration of GABA in the brain (by either enhancing GABA synthesis or blocking GABA metabolism), retigabine allosterically *[binding jargon...Zim'] potentiates GABA induced current in rat cortical neurons in a concentration-dependent manner."
And so on...Gawd, pdf files that lock up like that are a pain in the rear! Anyway, main thing here is...unless I am totally out of it, I myself did an extensive review of just this aspect on Retigabine and GABA and found that there was NO EFFECT ON GABA, and it was a non-issue!!! And this was from research info much more recently dated.
So geez Louise, now I'm going to have to go back and resurrect where the hell I got all that from, to see if I got it backwards, or these guys c/o India report are just "historical remnants" littering the side of the K channels road.
The relevance of this particular "GABA aspect" was hot on my to do list, as indeed, seemed like all/most of our trialees, and future trialee =ME, are on a Benzo!!! (= GABA party time in this particular synaptic dance). Thus a major Mmmmmmmmmmmmmmm????? thing. Well to me anyhow.
So again, if anyone else (particularly if not sleep deprived) wants to backtrack on this with me COOL! As I am still way behind in my "yet to do Retig. research" list.
Sorry, hope this is not too scatty of a post. [Hey, I'm down to 0.5 mg Clonazepam = 50% reduction in 10 days BUT 80%+ reduction in total sleep in 10 days! Not so cool..But so far no foaming at the mouth, white sweat Anxiety Horse with grinning Reaper skull on the back...Which is waaaaay cool. That guy is major she dog!]
Best, Zimichael
Just my personal experience that NAC didn't seem to do anything for me, ALA does. Tried with and without NAC.
Haven't had the SOTO treatment yet so can't tell you any more than Google. I do think my tinnitus may have been from an injury, so no reason to think it will help for other causes. But who really knows?
Sorry, back to Retigabine!
I came across this posting by Benryu in the Flupirtine thread. It is so informative,
I'd like to copy-paste it here: (thanks Benryu) bottom-line = retigabine might do the trick
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:
I'd like to copy-paste it here: (thanks Benryu) bottom-line = retigabine might do the trick
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 openers, 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 inter-spike 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)
- AUT00063 acts directly on the repolarization and is much more precise, so it's a viable solution providing it works as expected
this also caught my eye
http://time.com/105385/new-access-to-experimental-drugs-for-terminally-ill-patients/
Nationwide, people with a terminal illness for which available treatments aren't working can seek a Compassionate Use Exemption to be included in a clinical trial of a drug or procedure that might help them. Of the 550 requests the FDA received for such exceptions during the 2013 fiscal year, all were approved.
And with FDA approval averaging 11 to 14 years for a new drug, skipping the wait could mean a lot for someone who has only months to live.
This is all about our fundamental core right to life which is enshrined in constitutions all over.
It could be argued that some of us are on the terminal edge (Gaby Olthuis,etc ) and should be given
early immediate compassionate access to aut00063.
I personally believe that anyone going through a bad time with tinnitus should be given
access to drugs like 63 and this should be framed within the context of recent fast-track access legislation.
(I imagine Donald Trump's attorney would get it sorted before tea-time).
it's about time there was pressure to give us access. It would certainly do no harm to show compassion.
edit: added this juicy bit
http://www.nhs.uk/news/2014/03March/Pages/New-fast-track-drug-scheme-to-help-severely-ill.aspx
Commencing April 2014, the government has launched the Early Access to Medicines Scheme designed to help patients with life threatening or debilitating conditions get access to unlicensed medications that could potentially be of benefit at an earlier stage in their development than they would normally be available, and before they have been granted a licence. There also needs to be a medical need for these drugs, either because there are no other treatments available or the available treatments are not suitable (for example if the person has not responded to them).
The scheme does not replace the normal licencing process, but the early access scheme could allow access several years before the formal licence is granted. For example, the drug could be made available after phase II trials while phase III trials are still ongoing.
(sounds familiar?)
The drug only needs a PIM reference number. I believe the company merely has to
submit paperwork showing its drug could help people and one can then apply and should be fairly guaranteed to get it. Its a simple process when you look at it. and remarkably good timing.
Come on everybody, put your thinking caps on and let's see if we can get this stuff early.
(5 years early). We need positive input here. Could someone read the US & UK articles and come back with thoughts. We ALL tick ALL the boxes, so let's do what we can.
I don't know if this subject has been much discussed but it certainly warrants detailed discussion and increased awareness.
http://time.com/105385/new-access-to-experimental-drugs-for-terminally-ill-patients/
Nationwide, people with a terminal illness for which available treatments aren't working can seek a Compassionate Use Exemption to be included in a clinical trial of a drug or procedure that might help them. Of the 550 requests the FDA received for such exceptions during the 2013 fiscal year, all were approved.
And with FDA approval averaging 11 to 14 years for a new drug, skipping the wait could mean a lot for someone who has only months to live.
This is all about our fundamental core right to life which is enshrined in constitutions all over.
It could be argued that some of us are on the terminal edge (Gaby Olthuis,etc ) and should be given
early immediate compassionate access to aut00063.
I personally believe that anyone going through a bad time with tinnitus should be given
access to drugs like 63 and this should be framed within the context of recent fast-track access legislation.
(I imagine Donald Trump's attorney would get it sorted before tea-time).
it's about time there was pressure to give us access. It would certainly do no harm to show compassion.
edit: added this juicy bit
http://www.nhs.uk/news/2014/03March/Pages/New-fast-track-drug-scheme-to-help-severely-ill.aspx
Commencing April 2014, the government has launched the Early Access to Medicines Scheme designed to help patients with life threatening or debilitating conditions get access to unlicensed medications that could potentially be of benefit at an earlier stage in their development than they would normally be available, and before they have been granted a licence. There also needs to be a medical need for these drugs, either because there are no other treatments available or the available treatments are not suitable (for example if the person has not responded to them).
The scheme does not replace the normal licencing process, but the early access scheme could allow access several years before the formal licence is granted. For example, the drug could be made available after phase II trials while phase III trials are still ongoing.
(sounds familiar?)
The drug only needs a PIM reference number. I believe the company merely has to
submit paperwork showing its drug could help people and one can then apply and should be fairly guaranteed to get it. Its a simple process when you look at it. and remarkably good timing.
Come on everybody, put your thinking caps on and let's see if we can get this stuff early.
(5 years early). We need positive input here. Could someone read the US & UK articles and come back with thoughts. We ALL tick ALL the boxes, so let's do what we can.
I don't know if this subject has been much discussed but it certainly warrants detailed discussion and increased awareness.
Christian78
Member
- Dec 17, 2013
- 965
- Tinnitus Since
- (Sep 2013)
- Cause of Tinnitus
- progressive tinnitus, time of expiring in next 3-6 months
Yes i take trazadone that is 50mg of normal dosage300-600mg. I am just overly sensitive. I think I should take my pill after lectures not 2h before. Few days ago when i missed 2 dosages i did not got t increase but my sharpens returned.
I dont know why you fill people with misinformation, tell them then what medication more I use and explain how grave is that medication, if I use dosage of that antidepressant in quantity 8.33% of maximal dosage! Please stop babling around giving desinformation about me.
I just don't use maximum dosage of retigabine, and believe me if you would then you would not be able to do high level mathematics!!!!!!!!!!!!
Christian78
Member
- Dec 17, 2013
- 965
- Tinnitus Since
- (Sep 2013)
- Cause of Tinnitus
- progressive tinnitus, time of expiring in next 3-6 months
It depends on how do you feel. If you take retigabine it will not kill you on 3 months. So give it a try to 200mg and see, go easy and check urinary retention.
Christian78
Member
- Dec 17, 2013
- 965
- Tinnitus Since
- (Sep 2013)
- Cause of Tinnitus
- progressive tinnitus, time of expiring in next 3-6 months
Christian78
Member
- Dec 17, 2013
- 965
- Tinnitus Since
- (Sep 2013)
- Cause of Tinnitus
- progressive tinnitus, time of expiring in next 3-6 months
Deep and tough mathematical calculation, and also programming are so hard, you cant remember things, so you forget them fast. For ordinary people it means nothing but for those into deep stuff it means a lot.
I had hyperacusis for about a week after my tinnitus started. It was awful, and anybody who is living with it now has my sympathy.
On the bright side, from my own experience, I honestly think it's the same illness, just a slightly different presentation. I was listening to Louis Anderson (American comedian) on the radio this morning and he commented that living in Las Vegas is no fun for him anymore. He half jokingly said that the reason was the volume of the music in the clubs. Sound familiar? You'll find many people with tinnitus who avoid movies, sporting events, and similar crowded, noisy environments both out of fear of further auditory damage and due to a nasty little co-symptom that makes loud rooms stay loud not matter how long one stays in them. Used to be I could go to a wedding reception, say, and think, "Man, sure is noisy in here." Then five minutes later I wouldn't notice anymore. Just went to a good friend's reception in early August and found that the noise level, my discomfort at the noise level, and my virtual deafness due to the noise level, were all unchanged after hours and a good meal. I know it wasn't the same for everybody because I noticed some people hanging out in the side room where the speakers were amped up. Walking into that room was like walking into a hurricane to me. I ducked in just long enough to warn them about how dangerous it really was.
Earlier in the thread, our pioneering friend Mpt described going to some crazy event with revving engines and screaming rock music and feeling just fine. There's mixed feelings about how sensible that was, but it's the best evidence I've seen that retigabine can effect a cure (though we won't really know until some more people get on the drug and Mpt tapers off it). So, in my mind, it is equally likely to benefit hyperacusis sufferers as those with tinnitus and no/mild hyperacusis.
BTW, my hyperacusis went away after following the instructions in this video: . Take it slow like Dr. Hobbs suggests and expect to revisit this several days before full results. Hope it helps you too.
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