Discussion in 'Treatments' started by Danny Boy, Jul 12, 2015.
Separate names with a comma.
And it wasn't like that with trobalt?
Doesn't it say "becoming overexcited". Instead of "inhibiting already overexcited cells"?
I don't know why this thread is on "Treatments"-section when this is apparently just a leap of faith and hope...
Well, there are quite a few drugs in clinical trials that target the AMPA receptor.
It is known that in mammalian cochlea, glutamate mediates the neurotransmission between the inner hair cells and their afferent neurons. Glutamate stimulates three different receptor subtypes (AMPA, NMDA, Metabolotropic) in the post synaptic membranes. It is postulated that an impaired balance between the activities of the different receptor subtypes generates abnormal spikes perceived as tinnitus. Following this hypothesis, receptor pharmacological models for treatment of tinnitus have been established, intending tuning of the disturbed interplay of receptor subtypes by applying selective glutamate receptor antagonists. Improvement in the therapeutic success in tinnitus following the antagonistic drugs confirmed the validity of the concept, which has been further proven in clinical studies. Tinnex(Caroverine) is a quinoxaline-derivative with a direct antispasmodic action on smooth muscles as well as a calcium-antagonistic effect. The antispasmodic papaverine like effect is about ten times stronger than for papaverine for the same toxicity. Demonstrated in a series of clinical experiments that Tinnex is effective as a reversible glutamate antagonist in the excitatory afferent synapse of the cochlear inner hair cells. Glutamatergic receptors NMDA and AMPA have been considered to be instrumental in the toxicity of glutamate on the cochlear hair cells which causes tinnitus and hearing loss of otologic origin. A number of experimental studies and clinical trials of Tinnex have revealed that Tinnex can be used for the treatment of Cochlear synaptic tinnitus. The authors of various clinical studies have concluded that 63.3% of patients responding immediately to single-dose caroverine infusion treatment.
Again, dodging the point by quoting some text without addressing the issue I noticed.
And also it is interesting that you are quoting a text which talks about cochlear synaptic tinnitus and other threads you bash that in ear T and AM-101 is so 90s way to think.
Combinations comprising ampa receptor antagonists for the treatment of tinnitus
WO 2005049042 A1
The present invention relates to combinations suitable for the treatment of neurological disorders, in particular tinnitus. The combinations comprise at least one AMPA receptor antagonist and at least one compound selected from the group consisting of ant-anxiety drugs, antidepressants, antihistamines, anticonvulsants, vasodilators, zinc salts and anesthetics.
"COMBINATIONS COMPRISING AMPA RECEPTOR ANTAGONISTS FOR THE TREATMENT OF TINNITUS
The present invention relates to combinations suitable for the treatment of neurological disorders, in particular tinnitus.
Tinnitus is the medical term for roaring, buzzing, clicking, whistling, hissing, or high pitched ringing in the ears or inside the head. Tinnitus may be constant or occur intermittently in one or both ears. Although there are many theories about how tinnitus occurs, there is no scientific consensus to its origin. Some causes of tinnitus result from a blow to the head, large doses of aspirin, anemia, noise exposure, stress, impacted wax, hypertension and certain types of medications and tumors.
Surprisingly, it has been found that the effect of a combination which comprises at least one AMPA receptor antagonist and at least one compound selected from the group consisting of anti-anxiety drugs, antidepressants, antihistamines, anticonvulsants, vasodilators, zinc salts and anesthetics is greater than the additive effect of the combined drugs. Furthermore, the combinations disclosed herein can be used to treat tinnitus which is refractory to monotherapy employing one of the combination partners alone.
Hence, the invention relates to a combination, such as a combined preparation or pharmaceutical composition, which comprises at least one AMPA receptor antagonist and at least one compound selected from the group consisting of anti-anxiety drugs, antidepressants, antihistamines, anticonvulsants, vasodilators, zinc salts and anesthetics, in which the active ingredients are present in each case in free form or in the form of a pharmaceutically acceptable salt and optionally at least one pharmaceutically acceptable carrier; for simultaneous, separate or sequential use.
The term "AMPA receptor antagonists" as used herein includes, but is not limited to the quinoxaline-dione aminoalkylphosphonates of formula I"
Isn't all epileptic drugs to stop the cells from becoming overexcited? So what's your point?
My point is that T is already an overexcited state. So if the drug is designed to prevent this overexcited state instead of inhibiting an existing one - the effect may vary. I haven't read about this medicine etc. but I just thought that it would be good to think about this kind of things before posting to "Treatments"-section.
Imo this should be on "Alternative Treartments"-section because Perampanel has only "Danny Boy Approves"-stamp on it which is considered as a shot in the dark via googling. Your knowledge is just too shallow to compare AMPA antagonists.
When we have atleast some results we can consider moving it to "Treatments"-section. I have found only one research regarding AMPA antagonists and I believe the effect was really short if there was even any.
PS. You are actually quoting a patent application which may have never been filed. Nice source you have there.
Well, people did consider using it for tinnitus, so I don't know what you are getting at? And seriously? I am only trying to find things more safe vs trobalt. Seriously, why do you care so much? Nobody has tried it at higher doses. I would be willing to, but can't get a supply. And why don't you enlighten us about AMPA antagonists then?
It's not my job to enlighten us about AMPA antagonists. You started the thread in "Treatments"-section which has no disclaimers as Alternative-section has, you carry the responsibility.
This Perampanel/Fycompa might still be something to try. What if it's as effective as Trobalt, but as many has stated, with many less side-effects. Trobalt wasn't effective until you reached high dose and so far as I can see no one has tried higher doses of this med. Any news or updates about this?
there is literally no reason to suspect this drug will have any impact whatsoever on tinnitus. None. This was someone's fanciful speculation.
I think that riding a magic pony might cure tinnitus, but I'm not going to start a thread about it...
"As effective as trobalt", lol, another drug which has literally zero evidence to suggest that it's helpful with chronic T. Yes, we have some anecdotes to that effect -- we also have some anecdotes on here that lipoflavinoid, vitamin C, and prayer can reduce T.
Your statement is that Trobalt has ZERO evidence that could be helpful with t?
There is no clinical evidence to support the hypothesis that trobalt reduces the symptom of subjective tinnitus in humans or animals.
There is limited evidence to suggest that trobalt might reduce the risk of tinnitus occurring in animals following acoustic trauma -- but by itself, this is not compelling. The same thing has been demonstrated in humans using magnesium, among other things -- which have likewise not been shown to have much impact on chronic T once it has developed.
I am not suggesting this is a worthless line of inquiry, only that we are putting the cart well in front of the horse if we go around assuming that Trobalt is a useful tinnitus treatment in humans.
disclosure: I've experimented with trobalt, and would not discourage anyone else from doing so, provided they have consulted with a neurologist and are fully aware of the risks of the drug, the complete lack of evidence for efficiency, and the potential for long-term damage.
@linearb , I agree with that there isn't anything that shows that Perampanel works, which is true. But there is always worth a shot to try figuring out if it could be at least a relief. What you say about Trobalt isn't true, I would say. Yes the statements and anecdotes about Trobalt are few, but of all the treatments, meds and supplements that people here on TT has tried, Trobalt shows the most promise. I at least, can't find any other med on the forum that worked as good as it. Now, it has a lot of nasty side-effects, but the med makes sense in how it works. So in a way, you can say that it works for some and you can also say there is no evidence, depending on how you see it. But if you go through all the posts here on TT where people have written about their experiences with trying out Trobalt, many have had an effect, and that shows that something indeed happens. Trobalt might be a good base to develop new more pinpointed meds with less side-effects, like SF0034 (if I'm not mistaken).
I said there was no clinical evidence; there isn't. I admitted that there are anecdotal reports of people achieving a reduction in symptoms with it. The same can be said for benzodiazepines, which do actually have some clinical evidence along the same lines.
A few dozen people have reported their experience with Trobalt here. Even if if these anecdotes were controlled, blinded clinical data, it is still far too small a sample group to come to any significant conclusion about it.
I completely agree that the hypothetical model of tinnitus based on animal research into Kv channels, is an excellent reason to proceed with research along these lines, including more assessing more narrowly targeted drugs like SF0034 for potential therapeutic potential in tinnitus. I personally would stop well short of saying that this hypothetical model is a good reason for humans with tinnitus (and without uncontrolled epilepsy) to start experimenting with Trobalt, but I completely get that desperation and discomfort make us do irrational things sometimes. Like I said, I have taken Trobalt myself. I do not regret it, but I also will not claim that it was a rational decision based on a factual analysis. It was an emotional decision based on suffering and wanting to suffer less.
Thanks for your reply and info @linearb . That I agree on And yes, desperation does make us do desperate things. I haven't tried Trobalt myself but would consider it as a last resort if my T doesn't get better in maybe 6-12 months.
How did Trobalt effect you and your T?
Haha, I just wrote you a short novel here to answer your question
I have only experimented very briefly with it. The first time, I took 50mg TID, for one day only. On the second day, I had very strange, reactive tinnitus (which I rarely/never have otherwise) -- the sound of my own voice caused a shrieking scream in my left ear. This distressed me, so I discontinued immediately.
A few months later, out of, yes, desperation, I started up at 100mg TID. I proceeded at that dose for only 2-3 days. It did seem like the T was less intense/distressing, and, frankly, I rather enjoyed the sort of floaty/"out of it" sensation that I got for 30-40 minutes after each dose. However, on the third day, I suffered a recurrence of a chronic pelvic pain condition which I've had in the past, but which hadn't been a problem for a good number of years -- initially it just seemed like I was having trouble completely voiding my bladder (which was something I was prepared for, though it happened faster than I was expecting). However, over the 24 hours that followed, this changed, first turning into a nagging sensation of "having something stuck in my urethra", and then escalating into very, very significant pain -- pain bad enough that it actually made my tinnitus seem like a pretty small problem in comparison.
I discontinued the Trobalt at that point, but the symptoms continued for a number of weeks; ultimately, a combination of physical therapy, specific stretching, and warm baths seemed to resolve the symptoms.
I am in no way claiming that Trobalt caused this problem... I only took it for a couple days, and the rational skeptic in me thinks it's sort of unlikely that such limited, short-term use of a drug would cause problems like that which persisted for months afterwards. However, given my prior experiences with this kind of pelvic pain, I think it's reasonable to believe that my bladder muscles and genital nerves are hypersensitive and prone to misfiring. So, it does not seem impossible that Trobalt was "the straw that broke the camel's back" and pushed me over the edge into a flare-up. My urologist and primary care doctor both share that view. However, this incident did cause me to really look hard at the adverse incident reports surrounding Trobalt, and I came across one case study where a seizure patient developed severe urinary symptoms during Trobalt use, discontinued the drug, and became permanently unable to urinate without a catheter. So, that alarmed me -- this is a serious drug, for sure.
Whatever positive impact Trobalt had on my T (if it truly did, and was not just placebo) is not any more significant than the impact which benzos do. I know from lots of experience that if I take 15-20mg of Valium, my tinnitus is much less bothersome for the 2-3 days which follow... but I've so far been unwilling to take it more than very occasionally, because of the fear of long term damage and dependence. (I did actually take benzos for this and other reasons for a number of years, and the withdrawal process was absolutely harrowing). So, the thing which scares me off Trobalt at the moment is this thought: "I believe that valium is physiologically much safer than trobalt, and yet I am unwilling to take valium because I think it's too dangerous. So, how can I rationally justify prolonged Trobalt use?"
Again, this is just my personal judgement call, based on my personal experience. If I had taken Trobalt, seen the reduction in T and not had the severe pain/urinary problems, then I would almost certainly have tried to work my way up to 300mg TID for a couple months before tapering off to see if there was any long-term impact on my T. And, ultimately, that is what interested me in Trobalt -- the anecdotes on here from people who claim to have taken it for a while, and seen lasting improvement in their tinnitus following withdrawal from the drug. Dangerous drugs which can temporarily reduce tinnitus appear to be a dime a dozen to me (Klonopin, Sabril, etc) -- but none of these things have a lasting impact, for me, or for anyone else that I have polled.
That was a most excellent reply I must say! Very informative and something that everyone who considers taking Trobalt should read. The part about the person who couldn't pee without a catheter should be a clear warning (among all other side-effects) that this is not a drug to take lightly. And as you say, the attractive part about Trobalt is that some people have long lasting effects. The risk though...
I'm on Remeron 15mg myself. After a horror story and warning about benzos from a friend who still can't taper off completely after 10+ years, I will myself not take anything with that in it. I'm too sensitive as a person for that. I know it most probably would eat me up. Remeron works fine for sleeping and my mood is slightly better. The rest I'll try to manage with personal development like meditation, mindfulness and love from family and friends.
Have a great weekend all and I wish you all get better <3
I see now why u are putting Trobalt in same basket as Magnesium.
Sorry for your problems with Trobalt use (if they are even caused by trobalt, as I see u are not sure).
But u are making big mistake comparing trobalt effect and benzos effect. U say, "I have similar result with Valium", mate, mechanism of trobalt Vs Benzos is totally diferent. Trobalt do not make any gaba chemistry as Benzos, no one cured himself after 2 months of benzos, people that had luck did cured themself with 2 months of trobalt using. That's why effect after few days of use trobalt/benzos useless to compare. Trobal effect could last, even when u go off trobalt, benzos not.
Only statement that I am agreed with, is that there is not CLINICAL evidence for trobalt use in t. symptom. But, we are all here just because off that, there is stil no CLINICAL evidence for any drug that can cure t.
I am very happy about @Mpt @preslys that cured themselfs using Trobalt, and many others like @papu, @Juan Carlos @Danny Boy etc who some kind of permanent effect after using this drug. Togother with @Christian78 they are pionirs of this trial, and I hope that many other people (More than 200.000 that are reading trobalt thread) have had some kind o permanent decreasing of t volume.
Well -- we need to be a little careful here. Trobalt is a GABA-a agonist, same as benzos:
But, yes, RTG has Kv action and benzos do not.
As for "no one cured himself"... I remain to be convinced that anyone has actually cured themselves with RTG; as we agree, there's no clinical data to this effect. So, we're left with some anecdotes from people who think their subjective T is better now than it was before they took RTG. I can likewise find some anecdotes from people who took benzos for a while, and saw lasting improvement in their tinnitus over the same period... and of course, plenty of people see lasting improvement in their T during the first 6-24 months, without taking any drugs at all.
I would really like to believe that in at least some cases RTG can cause a permanent improvement in tinnitus, and I remain optimistic that one day we'll have some data to support that idea, either for RTG specifically or some other novel Kv drug, but I just don't think we can jump to that conclusion from the very limited anecdotal evidence that we have today.
But first of all "Retigabine works primarily as a potassium channel opener—that is, by activating a certain family of voltage-gated potassium channels in the brain" so I have no doubt that effect in t. suffers was because of this primary, that's why I do not compare effect of trobalt Vs benzos.
Personaly, I know person who lower his t to 15% of his baseline for a months on trobalt, so what u call anecdotal, is mainly real for me. Trobalt does something to t. What? How much? I do not know those answers, nobody knows, but it has strong impact in about 3/4 of suffers that have tried that.
To summarized, u know by your own that this drug is pretty dangerous, but u have decided to give a try. U would not play whit this fire thing if u hadn't strong believe that impact is real...maybe u should try for longer time, ignoring side effects for a little while...or maybe it could worse things in long term and your decison was correct...who knows
who knows, indeed! I don't disparage anyone for experimenting with Trobalt, we just need to be careful about leaping to conclusions.
by the way i am at 900 mg per day (300 mg tid) and i am doing extremly well, i am back enjoying life ciclyng and hiking and eating out and dancing again with my wife so thats why i have not written that mucho. I plan to write out report on sunday. I not cured by any chance but my tinnitus is down about 90% with a lot of zero moments up to 4 to 5 hours. I am just extremly afraid that when i stop taking trobalt it will go up again.
right now left ear zero. Right ear 1. pill taken at 5 am its 9 am here right now
does any one has prof stenoppapalopunus (i keep forgeting his last name) the guy from sf00034, i would love to email him with my four month trobalt experience.
Sadly he won't care one bit!
Thank for the email I will try anyway
Maybe better try prof Ernest Moore, he did study on rtg
He may be more interested in your experience
TT I find to be a very dry distant person
Is there anyone tried this? I'd love to do something for my tinnitus instead of suffering and hearing ''get used to it'' No I will f*cking not. Isn't it the reason why we do not have any cure yet?
And I don't know if this one will work but the latest news from the drug:
I'm consued. Is this drug out or the phases are not done yet? I'd do anything to try it.
I cant' say nothing about :/ Seems that for like an antagonist of glutammate. So probably it could be useful in acute phase but not a single word on Tinnitus so i don't know.
Trobalt work because it's a potassium channel opener not a "common" anti epilepsy drugs. Our brain it's very complicated. A lot of anti epilepsy drugs don't work on Tinnitus because the target isn't correct.
But if someone give it a try... good, we can say if work or not (but remember that we are very different and also Trobalt don't work for everyone).