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GABA-a Receptor Damage and Repair


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#1 VespeneGas

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Posted 28 January 2009 - 12:49 AM


A little background: about 3 weeks ago, I was floxed, which, for those of you who don't know, is a severe negative reaction to a quinolone antibiotic (ciprofloxacin in my case). Ciprofloxacin acts as a competitive antagonist at GABA-a receptors, which, acutely, can cause seizures. However, as a rare allergic case, I am still experiencing symptoms of GABA-a antagonism 3 weeks after discontinuation - difficulty sleeping, nonrestorative sleep, anxiety, tinnitus, shaking fingers. This leads me to believe that cipro is somehow still bound to my receptors (is this even possible?) or that it has destroyed many of my GABA-a receptors.

So, I'm wondering if anyone has any insight into whether the GABA system regenerates/repairs itself with time, and if there's anything (chemically) that I can do to expedite this process.

For teh brains, I currently supplement:
1. 100 mg choline citrate
2. 5g fish oil
3. 5 mg lithium aspartate.


Any knowledge or suggestions are greatly appreciated.

#2 StrangeAeons

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Posted 28 January 2009 - 01:55 AM

In my research into MAOI's I've discovered that Tranylcypromine (Parnate) causes an upregulation in GABA (B) over time; I couldn't tell you what that means for GABA (A), though. Of course, going on MAOI's is a fairly extreme measure to take if you're not depressed anyways. It looks like the coveted AMPAkines might upregulate GABA(a). I would be careful there, because benzodiazepenes appear to also upregulate GABA receptors after long term use, and yet the quality of the activity in these pathways appears to be diminished.
I know that by Duke's standards your fish oil dose is unusually high; he's been emphasizing that EFA's have a very long half-life in the body (~2 years) and that 2g should be the max. I also know that the preferred form of lithium on the forums appears to be lithium orotate, but I really couldn't tell you the theory behind that; you could do searches on both these issues, I'm merely aware of them.
I would try seeing a neuropsychologist or just out and out a neurologist if these symptoms persist. From the Wikipedia article it appears that this process can be rather involved and so I would want a professional looking at it.
As per the seizure threshold:
If you're seeing any bright lights or having odd smells, tingling sensations, etc then you may be having an aura for a seizure. Try to be in a place with isolation and padding; i.e. a large mattress with nothing you could hit nearby. Let people know if you seize to clear objects from the area but to not try and hold you still; and make sure you're not chewing or eating anything.

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#3 Matt

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Posted 28 January 2009 - 02:44 AM

I'd also really appreciate some help with this issue as well!

Restorative sleep for me took about 4 months to come back, but not fully. My sleep quality is still not where it should be. Since starting Calorie Restriction I had the best deepest sleeps of my life. But I never had insomnia in my life either. Then came along Cipro... Now I'm very easily woken up after my first sleep cycle. However I do feel quite rested and can feel normal in the days and can go on 14 hours until I'm tired. So massive improvement there. In my first few months of cipro toxicity is took me upto 5 hours to fall to sleep, and I would wake up every hour, every night.

I now fall to sleep within 5 minutes and I stay asleep for 5-6 hours, go bathroom and sleep for another 2 hours (make sure if you wake up in the middle of the night that you are not exposed to much light). I used to be able to stay sleep for 8 - 9 hours solid. Right now I'm starting up my Yoga again which is found to increase GABA levels by 30%.

There are a few MD's that were floxed and I can put you in touch with one of them if you want?

Heres one article on Quinolones and GHB as a treatment
http://aac.asm.org/c.../40/11/2573.pdf

Edited by Matt, 28 January 2009 - 03:43 AM.


#4 VespeneGas

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Posted 28 January 2009 - 04:30 AM

Heres one article on Quinolones and GHB as a treatment
http://aac.asm.org/c.../40/11/2573.pdf


I'd be happy to try it out [GHB is actually neuroprotective], but approaching my physician asking for GHB for an invisible problem sure does look like drug-seeking behavior. I know edward has had it prescribed to him before, maybe he can shed some light on how to acquire it short of going to your corner drug dealer. :p

Also, contact info for a floxed MD would be awesome; the credibility barrier would be a lot thinner. I've seen 2 GPs and a urologist since being floxed, and all they can say is "Wow! I've never HEARD of such an extreme reaction!" Sigh.

#5 Matt

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Posted 28 January 2009 - 04:54 AM

My doctor here in the UK believes the reaction I had is real, but its not treatable and the body-wide reaction won't be officially recognized for many years yet. You should like all other people hurt by quins report your reaction online to the FDA and Bayer. I hope you do this.

#6 desperate788

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Posted 28 January 2009 - 02:36 PM

My doctor here in the UK believes the reaction I had is real, but its not treatable and the body-wide reaction won't be officially recognized for many years yet. You should like all other people hurt by quins report your reaction online to the FDA and Bayer. I hope you do this.

any supplement or drug that strengthens gabaergic system generally?

#7 Imagination

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Posted 28 January 2009 - 10:21 PM

I don't know about fixing, but to increase I would go with theanine.

Other supplements are picamilion, phenibut, gaba and have a diet high in glutamic acid.

#8 StrangeAeons

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Posted 28 January 2009 - 10:31 PM

Increasing GABA might temporarily alleviate the problem, but receptor upregulation willl actually resolve it; therein lies the rub. Diminishing receptor sensitivity with more GABA ligands or flooding the receptors will probably make it harder to recover; we already know certain GABAergic substances like Phenibut, Benzodiazepenes, and alcohol cause tolerance; so the short term benefit is outweighed by the long term risks. I might investigate the AMPAkines, and if things get really bad the tranylcypromine might be worth consideration too.

#9 VespeneGas

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Posted 31 January 2009 - 08:10 PM

Increasing GABA might temporarily alleviate the problem, but receptor upregulation willl actually resolve it; therein lies the rub. Diminishing receptor sensitivity with more GABA ligands or flooding the receptors will probably make it harder to recover; we already know certain GABAergic substances like Phenibut, Benzodiazepenes, and alcohol cause tolerance; so the short term benefit is outweighed by the long term risks. I might investigate the AMPAkines, and if things get really bad the tranylcypromine might be worth consideration too.


heh, do you have a cheap, reliable source for any of the ampakines? CX717 preferred. :~

As per your analysis on GABAergic agents being counterproductive, I think you're probably right. I was reading a book on neural repair processes, and a GABA antagonist sped up the repair process in mice, while a GABA agonist slowed it down. Looks like the modafinil I was just prescribed might actually hasten recovery, but that's pure speculation really.

Any reliable products out there to boost BDNF levels? I can't exercise much at all because my joints and tendons are floxed pretty hard.

#10 StrangeAeons

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Posted 31 January 2009 - 11:24 PM

I'm not sure an out and out GABA antagonist (i.e. the benzo antagonist Flumazenil) would be such a good idea, as it appears your seizure threshold is already down; and if you have a seizure and your brain goes hypoxic or you get head trauma while flopping about on the ground, well... that would be somewhat counterproductive.
I might also look to ALCAR+®-ALA if you want to boost exercise performance; some also report marked improvement in that department with resveratrol. As per BDNF, I can't say for sure; I'd be wary of anything claiming to boost it without copious reliable data.
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#11 VespeneGas

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Posted 01 February 2009 - 01:01 AM

I'm not sure an out and out GABA antagonist (i.e. the benzo antagonist Flumazenil) would be such a good idea, as it appears your seizure threshold is already down; and if you have a seizure and your brain goes hypoxic or you get head trauma while flopping about on the ground, well... that would be somewhat counterproductive.
I might also look to ALCAR+®-ALA if you want to boost exercise performance; some also report marked improvement in that department with resveratrol. As per BDNF, I can't say for sure; I'd be wary of anything claiming to boost it without copious reliable data.


hehe, no, I'm not going to go out of my way to antagonize my GABA receptors (few people intentionally do things that decrease their sense of well-being) but I don't think going out and begging a script for a benzo off my GP is a good idea either.

Exercise performance isn't the issue, it's that I can't walk more than about a mile before one of my tendons starts in with the stabbing pain that says, "I will rupture if you don't stop." Cipro induces tendon-cell and chondrocyte apoptosis, so your tendons die and don't repair. It will be a long time before ALA + AlCAR will be of any (exercise-mediated) use to me. I think good sleep, good nutrition, and meditation will be my best bet here :~

edit: resveratrol inhibits angiogenesis and tendon repair. Probably a no-no right now.

Edited by VespeneGas, 01 February 2009 - 01:02 AM.


#12 unbreakable

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Posted 01 February 2009 - 07:56 PM

I would go for Flumazenil in combination with low-medium dose Phenobarbital, I doubt that supplements are as potent as the real deal.

Edited by unbreakable, 01 February 2009 - 07:58 PM.


#13 Mixter

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Posted 02 February 2009 - 08:40 AM

I would go for Flumazenil in combination with low-medium dose Phenobarbital, I doubt that supplements are as potent as the real deal.


Let's see, Flumazenil apparently can reverse receptor binding of benzos to GABA receptors, but again is a GABA-a antagonist,
side effect = anxiety. I'm unsure if you'd want that. Maybe worth a try indeed, but abort as soon as you notice any worsening.

Other than that, very interesting thread. So GABA antagonism is to blame for the horrible effects. The good aspect of
that is that some of the physical Cipro problems other than tendonitis might be psychosomatic/nervous then, and
you mainly need to fix the GABA receptors.

Here's what I personally would do in the case of screwed GABA: treat myself for classical anxiety / PTSD. Which means
1-2 weeks of benzos, followed by long-term GABA with valerian, theanine, lemon balm. May well be the acute 'floxing'
reaction is like an acute trauma that continues to cause anxiety, only it is not psychological but physical-neurological?
For people with anxiety/stress/trauma reactions, having additional physical symptoms which are actually psychosomatic,
would be typical. Also typical would be a disruption in GABA homeostasis. Hence why I would try a classical treatment for anxiety

Also, exercise.

Additionally: http://www.lef.org/p.../anxiety_02.htm

EDIT: pubmed link (no solutions, just description of GABA antagonism, sorry) http://www.pubmedcen...i?artid=1564969

Edited by mixter, 02 February 2009 - 08:46 AM.


#14 Matt

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Posted 02 February 2009 - 08:55 AM

You're saying taht the cipro may have screwed up the GABA receptors resulting in phsychosomatic symptoms (like anxiety), without experiencing any anxiety feelings? Because I can assure you that I had experienced many disturbing symptoms without any anxiety or depression. I've been far more anxious at earlier points in my life without experiencing anything like I went through after cipro.

Floxing symptoms tend to involve prolonged connective tissue problems (involving; bones, tendons, ligaments, muscles, vascular, teeth and skin), escalating nerve damage resulting in burning and tingling and sometimes numbness, ocular toxicity, CNS damage/distruption. It's a very complex picture. Benzo's seem to result in longer healing times in people who have been floxed.

Edited by Matt, 02 February 2009 - 08:57 AM.


#15 Matt

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Posted 02 February 2009 - 09:11 AM

I recommend you check these out

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http://health.groups...vors/message/36
http://health.groups...ors/message/117 (my story)
http://health.groups...vors/message/16
http://health.groups...ty/message/4658

#16 Mixter

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Posted 02 February 2009 - 10:18 AM

Sorry. "Psychosomatic" actually means stress/anxiety/masked anxiety (no major physiological difference between these), which could directly come
from disturbed GABA receptors, and also causes cortisol and other stress responses, which then further, real physiologic symptoms.
I believe it's a possible cause that should be ruled out by traditional treatment of anxiety/stress/trauma symptoms.

The insomnia would be a clasic symptom... If I'm right, you could measure cortisol levels though, and they should be well above 150 mcg/dl (usually
over the normal range, but maybe not for you taking into account healthy living & CR), even if well rested and relaxed.

Benzo's seem to result in longer healing times in people who have been floxed.


That's valuable information I didn't know, then benzos are not a good idea I guess. Perhaps treating the insomnia will resolve
(hidden) stress levels and improve the other symptoms. The LEF protocol suggests serious cases to get three different
non-benzo types of sleep aids (Ambien, Lunesta...) and cycle them, i.e. take a different one every night in order to avoid
tolerance building. Doing this for some weeks could be worth a try: http://www.lef.org/p...insomnia_01.htm

So benzos would be bad, perhaps just more unnatural receptor stimulation... but directly taking GABA otoh could still work,
even for the peripheral nervous system. If receptors are clogged or otherwise dysfunctional, increasing the neurotransmitter
should always work, at least a little, and at least not cause adverse reactions. I could be wrong, just $.02, but it seems logical.

Edited by mixter, 02 February 2009 - 10:18 AM.


#17 unbreakable

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Posted 02 February 2009 - 12:26 PM

It's not that easy, Flumazenil can eg. reverse prolonged benzodiazepine withdrawal... and if you use intravenous Flumazenil AND low-medium dose Phenobarbital for some time then there is no anxiety, that's basic psychopharmacology.

But if this quinolone antibiotic has irreversibly damaged your GABA-system (I don't know if it can) then you can just use symptomatic acting drugs like Benzos, Z-drugs, Mebrobamate, Carisoprodol, Phenobarbital, Picamilon, Phenibut, Baclofen (if the GABA-B system is damaged)... and wait for stem cell therapy or something like that.

I don't know if "floxing" is real and what exactly it should damage, but thinking "a potent neurotoxic reaction destroyed parts of my brain, I'll just pop some Taurine, Fish Oil, ALA & ALCAR and this will reverse it" is stupid, sorry. Drink some Methanol and then search for supplements to reverse the damage, good luck.

Edited by unbreakable, 02 February 2009 - 12:47 PM.

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#18 Matt

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Posted 02 February 2009 - 12:37 PM

The only people that were floxed that didn't see significant recoveries were mostly those with high prolonged doses of quinolones or some of the ones a few years back that were prescribed vioxx with a quinolone...


and




Now feel happy you never suffered a reaction like john and bob, and a few others like them.
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#19 VespeneGas

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Posted 02 February 2009 - 03:46 PM

I don't know if "floxing" is real and what exactly it should damage, but thinking "a potent neurotoxic reaction destroyed parts of my brain, I'll just pop some Taurine, Fish Oil, ALA & ALCAR and this will reverse it" is stupid, sorry. Drink some Methanol and then search for supplements to reverse the damage, good luck.


I can assure you that floxing is very real. I find it unlikely that I'm dreaming up crippling pain and ringing in my ears. Furthermore, I never implied that I would fix the damage using supplements, or that anything could fix the damage, ever. I came here looking for chemicals that might stimulate neurogenesis of GABAergic neurons (much like D3 agonists stimulate the differentiation of stem cells into dopaminergic neurons http://www.nature.co...ll/nrn1999.html ). I think my best bet is waiting and hoping, to be honest.

Snide, misdirected remarks like this aren't helping.

Incidentally, the ringing has lessened in the past couple days since doubling my lithium dosage to 10mg (elemental) per day, and cutting my caffeine intake. Either one could be pure coincidence, but here's hoping it's real progress.

http://www.ionchanne...p?pmid=11841566

#20 Matt

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Posted 02 February 2009 - 05:21 PM

If the damage or distruption wasn't able to be fixed. I wouldn't be almost 100% better :)

I went from perfect sleep all my life, can't even remember one night where I could not sleep. As far as I was concerned I was the best sleeper on the planet lol . Then after 1 cipro pill almost complete sleep onset + sleep maintenance insomnia. 5 hours to fall to sleep, waking up every 1 hour, waking up crying every night almost for 4 months from the terible literally end of world nightmares was having (my dreams involved a lot of nuclear bombs lol). 15 months later I can now sleep much better, I don't have nightmares, and only have sleeping issues 1 or 2 nights per month. It's not perfect, but I can fall to sleep within 5 minutes and stay to sleep for a while, then usually easily fall back to sleep. So obviously whatever went wrong with my CNS did resolve to a large extent. I have to stress I was not at all anxious during this time. Anxiety played no part in my insomnia or anything else.

Recovery can take upto 5 years for severe cases, 1-3 years for moderate causes and 6-12 months for mild. Floxing is certainly real, there is a yahoo group that have been reporting all this for 10 years now with thousands members who were injured while taking a quinolone.

I recovered almost 100% and so will you Ves.

Edited by Matt, 02 February 2009 - 05:23 PM.


#21 Matt

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Posted 02 February 2009 - 05:25 PM

Where did we get the name floxing from?

There was a book written with it, the women got floxed from 1 pill that changed her life completely.

Bitter pills
http://www.stephenfr...sbook_chp1.html

#22 stephen_b

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Posted 02 February 2009 - 08:32 PM

Ashwaghanda stimulates neurogenesis and is a GABA mimetic. Anyone think it might be helpful here?

StephenB

#23 unbreakable

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Posted 02 February 2009 - 09:23 PM

After reading some stuff and watching "The Curious Case of Benjamin Button" I now know what cures floxed people - it's a highly limited resource, but extremely powerful -> E.M.I.T.

Edited by unbreakable, 02 February 2009 - 09:24 PM.


#24 VespeneGas

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Posted 03 February 2009 - 05:13 AM

Ashwaghanda stimulates neurogenesis and is a GABA mimetic. Anyone think it might be helpful here?

StephenB


I've been taking Jarrow Ashwagandha every night for 2 months for sleep. It seems to help in that capacity, I hope it's behind the scenes repairing some axons and dendrites and whatnot, but who can say, really?

Also, wtf is E.M.I.T? A joke I presume.

#25 unbreakable

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Posted 03 February 2009 - 06:34 AM

Time

#26 bgwithadd

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Posted 04 February 2009 - 08:00 AM

Maybe an NDMA antagonist? It should keep you from getting overwhelmed and let your system cool down a bit. Anything direct on gaba right now might do more harm than good. On the other hand, gabapentin is both anxyolytic and repairs brain damage. So, that might be a better bet.

Edited by bgwithadd, 04 February 2009 - 08:28 AM.


#27 VespeneGas

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Posted 07 February 2009 - 03:06 AM

Maybe an NDMA antagonist? It should keep you from getting overwhelmed and let your system cool down a bit. Anything direct on gaba right now might do more harm than good. On the other hand, gabapentin is both anxyolytic and repairs brain damage. So, that might be a better bet.


Hmmmm... wikipedia lists ethanol as an NMDA antagonist, but when I had 3 drinks the other night for my friend's bday, the tinnitus got worse. Confusing. Most of the others on the list (methadone, ketamine, etc) seem kinda illegal, unless I can get some memantine or chug cough syrup (Dextromethorphan) (j/k about the cough syrup of course). Any suggestions?

Also, I'd never heard that gabapentin repairs brain damage. Any resources I might check out on this?

Thanks for the suggestions.

#28 unbreakable

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Posted 09 February 2009 - 12:13 PM

L-Baclofen is probably the perfect agent for the GABA/tinnitus connection. As it is not available, maybe Baclofen helps too?

#29 bgwithadd

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Posted 09 February 2009 - 02:47 PM

There's magnesium for starters, also very calming. Also memantine and amantadine. I am not sure where I read about gabapentin healing neurons but it's used for meth addicts to give them deep restful sleep and repair their brains a bit. Of course, going off it might be almost as bad as getting floxed, but if you gradually decreased the dose it might be worth it.

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#30 tlm884

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Posted 09 February 2009 - 02:54 PM

To help with the tendons you might consider a nicotine patch. Nicotine has been shown to increase angiogenesis.

Lithium Orotate also causes growth of the prefrontal cortex (thus neurons??)

Edited by tlm884, 09 February 2009 - 02:56 PM.





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