BMS-204352 Maxipost — Modulating Potassium Ion Channels Decreases Tinnitus in Rats

[mock turtle]

id put my money on this approach

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Effects of the potassium ion channel modulators BMS-204352 Maxipost and its R-enantiomer on salicylate-induced tinnitus in rats.

Lobarinas E, Dalby-Brown W, Stolzberg D, Mirza NR, Allman BL, Salvi R.
Source

State University of New York at Buffalo, Center for Hearing and Deafness, Buffalo, NY 14214, United States. el24@acsu.buffalo.edu

 

[Jon Wayne]

id put my money on this approach

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i wouldn't, taking anticonvulsant drugs with so many potential side effects isnt appealing

 

[mock turtle]

John Wayne

you raise an interesting point

im gonna have to re read the article again because my "take away" wasnt that the research indicated treatment with oral administration of anticonvulsants

i was thinking that administration of maxipost to inhibit BK channels might be local (intra cochlear)

btw heres some info from wikipedia regarding big potassium channels

"BK channels are pharmacological targets for the treatment of stroke. Various pharmaceutical companies developed synthetic molecules activating these channels[11] in order to prevent excessive neurotoxic calcium entry in neurons.[12] But BMS-204352 (MaxiPost) a molecule developed by Bristol-Myers Squibb failed to improve clinical outcome in stroke patients compared to placebo.[13] BK channels have also been found to be activated by exogenous pollutants and endogenous gazotransmitters carbon monoxide [14][15] and hydrogen sulphide.[16]
BK channels are blocked by tetraethylammonium (TEA), paxilline[17] and iberiotoxin.[18]"

hydrogen sulfide ?..are trace amounts found in some wine and foods and i wonder if that ups tinnitus??

i have read that anticonvulsants target voltage-gatedcalcium channels sv2a and α2δ (what ever they are...im not smart enough to know) but a quick web search indicates YOU ARE RIGHT that BK channels can play a role in epilepsy and thus presumably some oral medications target BK accordingly

but apparently, calcium channels and gaba ligands are primarily the focus of many, if not most anticonvulsants

just the same you raise an interesting point

best wishes
mock turtle

 

[joe]

Hello, well you was right to put your money on Maxi Post, however its too Toxic for humans, but I have found that Retigabine (trobalt) works in similar ways, Potassium channel openers are looking to be a potential cure in tinnitus

http://www.dailymail.co.uk/health/a...loping-drug-treatments.html?ito=feeds-newsxml


http://www.sciencedaily.com/release...ily/mind_brain/tinnitus (ScienceDaily: Mind &

 

[Tha_b_man]

Wish I was a rat...

 

[Mpt]

does anyone know if this drug ever made it to market... I could find information online regarding phase 3 trials, but I haven't been able to find any other information on it-- it is a potassium channel drug

 

[bill 112]

Autifony is taking this approach,they even mention Maxipost in their literature.Buying a new laptop soon so hopefully will be able to post links to this stuff.Google Autifony and in one of their writings they specifically mention and refer to Maxipost.

 

[Mpt]

bill- do you know if maxipost made it past stage 3 trials -- I believe its an epilepsy drug-- when I google maxipost it seems like its not a medication that is currently available

 

[bill 112]

To be honest Mpt im not quite sure but I dont believe it did,no mention of it anywhere but aut00063 is derived from it and follows the same basic principal but in a more accurate manor.

 

[cdog]

http://www.ncbi.nlm.nih.gov/pubmed/21640740

So drugs that inhibit tinnitus by acting on the KV3.(1-7) family in animals/humans :

Lidocaine
Retigabine
R-Maxipost
Aut00063

promising...

Has anyone looked into Maxipost? Is it obtainable anywhere? (Perhaps here : http://www.tocris.com/dispprod.php?ItemId=383718 )?

 

[SoulStation]

Has anyone looked into Maxipost? Is it obtainable anywhere? (Perhaps here : http://www.tocris.com/dispprod.php?ItemId=383718 )?

Don't think it's available ...

 

[cdog]

Don't think it's available ...

If you go to that link and select the country (e.g. USA), it says it's available and you can buy either 10mg or 50mg of it.

Mpt was asking about it here : https://www.tinnitustalk.com/threads/bms-204352-maxipost-—-modulating-potassium-ion-channels-decreases-tinnitus-in-rats.258/

I guess that was before he tried Retigabine.

 

[111]

If you go to that link and select the country (e.g. USA), it says it's available and you can buy either 10mg or 50mg of it

If you look at the certificate of analysis for this product and another one similar ML 277 it says this at the bottom of each page ?

Caution - Not Fully Tested • Research Use Only • Not For Human or Veterinary Use

 

[cdog]

If you look at the certificate of analysis for this product and another one similar ML 277 it says this at the bottom of each page ?

Caution - Not Fully Tested • Research Use Only • Not For Human or Veterinary Use

Yeah, but most if not all drugs are like that before a Phase I trial on humans - no one knows how humans will respond. (Although I guess more careful experimentation is done on animals prior to that).

On the other hand (and I brought up this example before), there are people like Alexander Shulgin, who have been trying out completely new synthesized substances, and were not afraid... (at least not enough to not do it).

 

[Zimichael]

Has anyone looked into Maxipost? Is it obtainable anywhere? (Perhaps here : http://www.tocris.com/dispprod.php?ItemId=383718 )?

...Well, this sure is a creative thread!

On Maxipost, rather interesting to note - yet another WTF???...with Tinnitus:

Unexpectedly, the R-enantiomer *[ sort of mirror image opposite ~ Zimichael] of Maxipost, R-Maxipost, which has no anxiolytic effects and negatively modulates Kv7.2-Kv7.5, also suppressed behavioral evidence of tinnitus. Our original hypothesis was that Kv7.2-Kv7.5 channels might play a key role in tinnitus generation and that Maxipost but not R-Maxipost would suppress tinnitus; however, it appears that a shared mechanism between Maxipost and R-xMaxipost, such as inhibition of Kv7.1 channels or activation of BK channels or some novel mechanism common to both compounds, underlies salicylate induced tinnitus as both compounds completely abolished behavioral evidence of tinnitus in a dose-dependent manner.

Basically as I understand this in simple English..."If you kick the door (K channels) down, you get a positive effect. If you close the door (K channels) and bolt it, you get a positive effect." I mean WTF?????? That's like saying if your turn the power off the light goes on. If you turn the power on, the light goes on. Just goofy...But what's new with T huh?!

The price of this stuff is gold bars if you need 900 mg a day. Note price of $779 for 50 mg:

Makes Potiga look cheap...and tested on humans!

Creative though... Zimichael

*(Yeah, yeah....1:30 am California time, but that thing called "sleep" seems to become a chimeric memory on a Benzo taper. For me anyhow. Nearly two weeks of this kukka...Sigh!)

 

[xanaxvictim]

Actually it seems that Maxipost (BMS-204352) had indeed been tested on human subjects, who are stroke patients

In healthy humans, single and multiple i.v. doses of BMS-204352 (0.001 to 0.2 mg/kg) were safe, well-tolerated and without psychomotor function effects. Multiple doses of BMS-204352 (0.1–2 mg/kg i.v.) administered within 48 h after stroke onset were well tolerated in patients in Phase II studies, designed to evaluate safety, tolerability and pharmacokinetics. No clinically significant differences in organ toxicity or adverse effects were found, and total clearance and volume of distribution were independent of dose. BMS-204352 failed to show superior efficacy in acute stroke patients compared to placebo in a Phase III study that included 1978 patients at 200 centers worldwide.

http://onlinelibrary.wiley.com/doi/...ionid=DAC3DF02FA9A9ED8154FA70D27C9F2CA.f04t02

No effect on stroke patients, but no one have tested it on T patients yet, any lab rats (Oh but it's d..n expensive, maybe someone can call a Chinese/Indian chemical company to make some)?

Method of synthesis
http://www.sciencedirect.com/science/article/pii/S0960894X02001014