Memberwell it looks like you are only going for 300mg/day for the next two months? Any plans to increase dosage? 84 X 100 mg / 28 = 300/day
Retigabine (Trobalt, Potiga) — General Discussion
- Thread starter Mpt
- Start date
well it looks like you are only going for 300mg/day for the next two months? Any plans to increase dosage? 84 X 100 mg / 28 = 300/day
SoulStation
Member
@locoyeti
I really want to but my GP won't prescribe me more because he really doesn't know the drug. I am grateful he prescribed it so I didn't ask him more then once. I would like to see a neurologist but I don't know why any neurologist would just see me, a random patient who he/she doesn't know, and prescribe me more of an off-label epilepsy medication at a higher dosage. I suppose maybe he would consult with my GP but I have a feeling that he would just tell me no and give me something else like Gabapentin or Tetragol.
@dochoppy
Yes. This med has lowered T in a few cases (including me). For me it seems to get rid of the central "Head" t which seems to radiate around my head and get aggravated by exercise and reduce the occurrence of "spikes". I feel like for myself I have reached a plateau in my progress with Potiga unless I up my dosage.
@Mpt , @Christian78 , @Johno, myself, and a few others have experienced some positive results. I have had some very good moments while on this drug, but then again I am a unique case. It was an interesting observation that I seemed to have similar results to @Johno and we both seem to have noise induced T somewhat near the same frequency.
SoulStation
Member
@dochoppy
there were two people on hear who said the T / H got a little bit worse with the Potiga.
@Zimichael, @Hengist
Look for the the thread Retigabine (Trobalt, Potiga) — User Experiences
there were two people on hear who said the T / H got a little bit worse with the Potiga.
@Zimichael, @Hengist
Look for the the thread Retigabine (Trobalt, Potiga) — User Experiences
found a very good January 2014 paper that specifically compares Retigabine, Flupertine, and two other BK channel modulators on their effectiveness with regard to tinnitus:
http://www.ncbi.nlm.nih.gov/pubmed/24681057
It's not a public paper so I will try and summarize it for those that can't access it.
excerpts / interpretations:
"For retigabine, the EC50 (8.0 8μM) determined in this study was comparable, though slightly higher, than the EC50 for KV7 subtype current activation (0.6–6.2 8μM; nH roughly 1.0 for each subtype; Tatulian et al., 2001). Retigabine at this concentration range induced observable network inhibitory effects"
[The EC50 they got for Retigabine was 8μM. Interesting to point out that the Tatulian paper (https://www.ucl.ac.uk/npp/research/dab/dablab/Tatulian_et_al_2001.pdf) had specific EC50 values for each channel that were lower.]
"Even at low concentrations (1.0–2.0 μM), rapid inhibitory effects on network spike and burst rates were observed for all four drugs, although they often required up to 15 min of stabilization. A decrease in spike and burst activity under retigabine and flupirtine at high concentrations ( > 10 μM) was almost instantaneous "
[pretty potent stuff]
"The stabilized activity levels (spike rate) recorded 1.0 h after the wash were quantified as percent of the reference activity before drug applications. Retigabine and flupirtine both exhibited full recoveries near 100%:"
[Even after application of 50μM solution, after the washout period the activity came back completely normal. This is good in the sense that there is no lasting damage to the cells (the other two BK channel modulators did not have full recoveries), but it also means that it is possible that there might not be lasting improvement, unless some secondary homeostatic plastic mechanisms bring the network back to the previous non-tinnitus state.]
"However, modulations of action potential duration, as reflected in peak maxima positions, followed a different pattern. Retigabine shortened the duration by 9.5715% (P<0.0001), while flupirtine did not cause a change ."
[from my understanding this would be a beneficial effect for the high frequency firing neurons in the auditory cortex].
on flupertine:
"In this study, we found that flupirtine was twice as potent in its inhibitory effect on the auditory cortical networks as retigabine (4 μM vs. 8 μM), and exerted significantly different effects on extracellular action potentials. This is perhaps due to other mechan- isms of flupirtine at comparable concentrations, such as the effect on the G-protein coupled inwardly rectifying K current at the EC50 of 0.6 μM (Jakob and Krieglstein, 1997), or the potentiation of GABAA current at<10 μM (Klinger et al., 2012). Expectedly, we observed a significant GABAergic effect of flupirtine, as the EC50 increased 6-fold under the presence of the GABAA blocker pentylenetetrazol, an effect of which was not apparent for retigabine."
[flupertine does some interesting stuff, but for our purposes is not as good as retigabine, and that is due to the Therapeutic dosage graph below]
[Nat is the natural rate of fire, PTZ, is the drug they used to simulate tinnitus, and the x axis shows the μM of retigabine (RTG) and flupertine (FPT) respectively. FPT has a pretty steep sigmoid curve, and doesn't show any activity till you get well past 5 μM. retigabine shows its effects almost immediately from 1 μM.]
finally:
"We estimated the therapeutic potential of K channel openers in suppressing tinnitus-like activity by quantifying the responses in the auditory cortical networks. Retigabine had the highest therapeutic potential, with a therapeutic concentration of 7.4 μM – a concentration at which counteraction against induced- hyperactivity were effective – followed by NS1619 (15.2 μM), flupirtine (23.3 μM), and isopimaric acid (30.0 μM). These values were well within the range of their effective concentrations against epilepsy (3–100 μM; Kobayashi et al., 2008), thus, possible off-label treatment for tinnitus is plausible (and safe). Clinical studies had calculated the free brain concentration of retigabine taken at 1200 mg/day to be around 2.0 μM (Large et al., 2012) "
[sounds pretty awesome to me!]
More thoughts on dosage:
The general consensus is the epilepsy is a genetic disease, so retigabine was intended to be taken for very long periods of time (years). I don't think that is the case with us, as tinnitus is not genetic and is probably just reversible hyperactivity of neurons, that may plausibly cured. I don't think the dosage schedule of retigabine for epilepsy is optimal. if you look at the data above, it is clear that a sufficient dosage is required to do any real work. Here is another graph from that paper:
I am of the opinion that 900mg/day is the very least that someone should try. I don't see any reason not to try 1200mg/day, if it will get one to the 2μM brain concentration. There were some issues with taking this drug at very high dosages, I recall from the australian report that out of 6 healthy volunteers that took a one-time dosage of 900mg (in one sitting), 2 of them had some heart arrythmias that went away after a few hours (this might be the slight effect on Kv7.1 at very high dosages), but I am not advocating 900mgX3 = 2700mg/day, but at least something high enough to get some effect. And I don't think that taking this drug forever is a good idea, although if one were optimistic that a better solution will come around in the next 5 years, I suppose it would not be too big a deal if some people were deciding to take retigabine for the foreseeable future in anticipation of something better. But hopefully the effect of this drug at a high enough dosage will induce permanent reset and we can kiss tinnitus goodbye.]
http://www.ncbi.nlm.nih.gov/pubmed/24681057
It's not a public paper so I will try and summarize it for those that can't access it.
excerpts / interpretations:
"For retigabine, the EC50 (8.0 8μM) determined in this study was comparable, though slightly higher, than the EC50 for KV7 subtype current activation (0.6–6.2 8μM; nH roughly 1.0 for each subtype; Tatulian et al., 2001). Retigabine at this concentration range induced observable network inhibitory effects"
[The EC50 they got for Retigabine was 8μM. Interesting to point out that the Tatulian paper (https://www.ucl.ac.uk/npp/research/dab/dablab/Tatulian_et_al_2001.pdf) had specific EC50 values for each channel that were lower.]
"Even at low concentrations (1.0–2.0 μM), rapid inhibitory effects on network spike and burst rates were observed for all four drugs, although they often required up to 15 min of stabilization. A decrease in spike and burst activity under retigabine and flupirtine at high concentrations ( > 10 μM) was almost instantaneous "
[pretty potent stuff]
"The stabilized activity levels (spike rate) recorded 1.0 h after the wash were quantified as percent of the reference activity before drug applications. Retigabine and flupirtine both exhibited full recoveries near 100%:"
[Even after application of 50μM solution, after the washout period the activity came back completely normal. This is good in the sense that there is no lasting damage to the cells (the other two BK channel modulators did not have full recoveries), but it also means that it is possible that there might not be lasting improvement, unless some secondary homeostatic plastic mechanisms bring the network back to the previous non-tinnitus state.]
"However, modulations of action potential duration, as reflected in peak maxima positions, followed a different pattern. Retigabine shortened the duration by 9.5715% (P<0.0001), while flupirtine did not cause a change ."
[from my understanding this would be a beneficial effect for the high frequency firing neurons in the auditory cortex].
on flupertine:
"In this study, we found that flupirtine was twice as potent in its inhibitory effect on the auditory cortical networks as retigabine (4 μM vs. 8 μM), and exerted significantly different effects on extracellular action potentials. This is perhaps due to other mechan- isms of flupirtine at comparable concentrations, such as the effect on the G-protein coupled inwardly rectifying K current at the EC50 of 0.6 μM (Jakob and Krieglstein, 1997), or the potentiation of GABAA current at<10 μM (Klinger et al., 2012). Expectedly, we observed a significant GABAergic effect of flupirtine, as the EC50 increased 6-fold under the presence of the GABAA blocker pentylenetetrazol, an effect of which was not apparent for retigabine."
[flupertine does some interesting stuff, but for our purposes is not as good as retigabine, and that is due to the Therapeutic dosage graph below]
[Nat is the natural rate of fire, PTZ, is the drug they used to simulate tinnitus, and the x axis shows the μM of retigabine (RTG) and flupertine (FPT) respectively. FPT has a pretty steep sigmoid curve, and doesn't show any activity till you get well past 5 μM. retigabine shows its effects almost immediately from 1 μM.]
finally:
"We estimated the therapeutic potential of K channel openers in suppressing tinnitus-like activity by quantifying the responses in the auditory cortical networks. Retigabine had the highest therapeutic potential, with a therapeutic concentration of 7.4 μM – a concentration at which counteraction against induced- hyperactivity were effective – followed by NS1619 (15.2 μM), flupirtine (23.3 μM), and isopimaric acid (30.0 μM). These values were well within the range of their effective concentrations against epilepsy (3–100 μM; Kobayashi et al., 2008), thus, possible off-label treatment for tinnitus is plausible (and safe). Clinical studies had calculated the free brain concentration of retigabine taken at 1200 mg/day to be around 2.0 μM (Large et al., 2012) "
[sounds pretty awesome to me!]
More thoughts on dosage:
The general consensus is the epilepsy is a genetic disease, so retigabine was intended to be taken for very long periods of time (years). I don't think that is the case with us, as tinnitus is not genetic and is probably just reversible hyperactivity of neurons, that may plausibly cured. I don't think the dosage schedule of retigabine for epilepsy is optimal. if you look at the data above, it is clear that a sufficient dosage is required to do any real work. Here is another graph from that paper:
I am of the opinion that 900mg/day is the very least that someone should try. I don't see any reason not to try 1200mg/day, if it will get one to the 2μM brain concentration. There were some issues with taking this drug at very high dosages, I recall from the australian report that out of 6 healthy volunteers that took a one-time dosage of 900mg (in one sitting), 2 of them had some heart arrythmias that went away after a few hours (this might be the slight effect on Kv7.1 at very high dosages), but I am not advocating 900mgX3 = 2700mg/day, but at least something high enough to get some effect. And I don't think that taking this drug forever is a good idea, although if one were optimistic that a better solution will come around in the next 5 years, I suppose it would not be too big a deal if some people were deciding to take retigabine for the foreseeable future in anticipation of something better. But hopefully the effect of this drug at a high enough dosage will induce permanent reset and we can kiss tinnitus goodbye.]
- Mar 18, 2014
- 58
- 48
- Tinnitus Since
- 3/2010
- Cause of Tinnitus
- Noise exposure, drug combo?
Wow, thats great info, can't believe they actually mention drugs for tinnitus, that is so hopeful.
all the quotes come from the link at the beginning of the post:
http://www.ncbi.nlm.nih.gov/pubmed/24681057
it is not a public paper though. you'll either have to pay for it, or get access to scientific publications, directly or indirectly.
SoulStation
Member
@Zimichael
I just checked my blueskydrugs account and as of 10/15/2014 my order status has changed to "shipped"...
I just checked my blueskydrugs account and as of 10/15/2014 my order status has changed to "shipped"...
@locoyeti thats awesome info, besides, that could help people get a Retigabine prescription from doctor if have the PDF. Im not asking to upload as public file but maybe email to some of us? we have nothing 'official' to show to our doctors. Mentioning an "internet forum" doesnt sound reliable for them
theekarwash
Member
- Jun 22, 2014
- 158
- Tinnitus Since
- 05/2014
- Cause of Tinnitus
- Noise and/or Ear Infeciton
If anyone needs that paper, here it is:
http://www56.zippyshare.com/v/32289713/file.html
If it is not allowed to share links, sent me a PM.
http://www56.zippyshare.com/v/32289713/file.html
If it is not allowed to share links, sent me a PM.
So I went to my doctor today and she wouldn't prescribe me with trobalt as it isn't licensed for tinnitis...I pleaded and bagged telling her it would change my life, save it even, all she said was, she wasn't allowed to prescribe it to me. This is exactly the reason I want to die, because there's no help....
Hey Danny Boy. Sorry to hear that. You are not the first on this thread to hit a brick wall trying to get Retigabine from a doctor. What i don't get, is it is developed here! It comes down to having a valid prescription and getting an understanding doctor. In your case, sadly, not. Are you able to see a different doctor that can refer you to a neurologist? Download and print the pdf on Retgabine above (or any supporting docs) and see if they will budge when reading it as proof Retigabine can work for T. They need a reason to prescribe it off-label.
To other Forum members, I realize that this thread is about Retigabine but I am really worried about Danny Boy and hope you don't mind this one off topic post from me.
Danny Boy, many of us have had the same feelings at times that you are having now. Also, many of us needed an AD (antidepressant) to pull us out of that state of despair that you are now in. If you are not already on an AD please see your doctor ASAP about it!! If you are already on one, it's obviously not doing the job at the current dosage. Talk to your doctor about either a dosage increase or trying a different AD.
When your anxiety level is reduced, it's likely that the severity of your T will diminish also, as mine did. Acute anxiety exacerbates a T condition. You need to address your anxiety issue now! Please don't put it off.
Good Luck!
Danny Boy, many of us have had the same feelings at times that you are having now. Also, many of us needed an AD (antidepressant) to pull us out of that state of despair that you are now in. If you are not already on an AD please see your doctor ASAP about it!! If you are already on one, it's obviously not doing the job at the current dosage. Talk to your doctor about either a dosage increase or trying a different AD.
When your anxiety level is reduced, it's likely that the severity of your T will diminish also, as mine did. Acute anxiety exacerbates a T condition. You need to address your anxiety issue now! Please don't put it off.
Good Luck!
Hi every Retigabine user, I am able to purchase it in bulk form from an API manufacturer ,
I have brought a mini weight scale that with accuracy up to 0.01g (10mg) .
May I know what is the safest and maximum period for taking the drug continously without side-effect ( especially on the pigmentation of retina or nail etc.)
I have brought a mini weight scale that with accuracy up to 0.01g (10mg) .
May I know what is the safest and maximum period for taking the drug continously without side-effect ( especially on the pigmentation of retina or nail etc.)
read this document for the info you will need.
www.tga.gov.au/word/auspar/auspar-retigabine-131017.docx
also what supplier did you use, can you let us know at all ?
is it this one by any chance at all, I got prices off them recently, never went ahead with the purchase, but could be a way of getting this stuff for sure, if I change my mind !
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
- Dec 24, 2013
- 933
- Tinnitus Since
- (1956) > 1980 > 2006 > 2012 > (2015)
- Cause of Tinnitus
- Ac. Trauma & Ac.Trauma + Meds.
Hell's bells...what a name! Merry Chemical...This stuff may be LSD for all I would know.
Good luck matey, but count me out on this source. I have a hard enough time trusting that "wild caught" salmon as a "Product of China" in my local Safeway is indeed salmon; wild caught; and a product of the 'Middle Kingdom'. Pray do they even have salmon in Chinese waters??? Could there be any left??? At least it looks like fish...but a white powder called "Retigabine"???
Braver than me by a long shot!
Z.
some info on a product targeting the KV3.4 channel, might be of interest
http://www.sigmaaldrich.com/catalog/papers/9506974
http://www.sigmaaldrich.com/catalog/papers/9506974
Thank you for finding the paper, @locoyeti ! Just a question on the data bolded above - if the effective therapeutic concentration is 7.4um and at 1200mg/day you only get to 2.0um, it seems that it would require 7.4/2.0 * 1200 = 4320 mg/day of retigabine to get the the therapeutic concentration. This would seem to conflict with the "plausible and safe" assessment above, as I don't believe retigabine has been tested at such high dosages in epilepsy trials. Am I misunderstanding something here?
They are either saying that you don't have to go up that high to get an effect, or that going up that high hasn't been proved to be dangerous. From what I remember, the literature says t stop at 1200mg because no further beneficial effects were shown as an adjunct seizure treatment. It didn't say definitely that more side effects would occur. But I'm with you in being cautious. That is a heavy dose!
jeannie
Member
- Nov 2, 2013
- 429
- Tinnitus Since
- 2013
- Cause of Tinnitus
- Noise-induced, Ear Infection, Medication... Who knows?
these doctors should prescribe this medicine if someone is willing to risk the side effects!!! people commiting suicide and begging for help. let them try it doctors!!
wow, is this that easy? anyone can buy Retigabine like this? if some brave guy test it and nothing strange happens, and even it works, that will mean we have make disappear a big barrier for most of us wich is getting the prescription
Then, if this is powder, after weighting it should be put into an empty capsule to take in or its safe to mix with water and drink? another posible good thing of this is avoiding the supply problems that forzed some to stop the treatment and not reach the desired dosage. Anyone else have an idea about how trustable can be this?
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