Pubmed - Vasopressin exposure in rats - Kidney/Ear relationship

Hey..Sorry to keep bumping, but I just found a little bit more about the drug treatment I was referring to.

They're called "aquaretics" ...as opposed to diuretics ....... They don't cause electrolyte imbalance like diuretics can, because they simply affect water absorption

Here's something that just came up on pubmed if anyone is interested.

Aquaretic Agents: What's Beyond the Treatment of Hyponatremia?
"Unlike the more commonly used diuretics, aquaretic agents can induce an increase in urinary volume without incurring a loss of electrolytes. These molecules belong to a family of vasopressin receptor antagonists, V2 in particular, that regulate optional renal water re-absorption via the synthesis and expression of aquaporin-2. In view of their properties, they have become the agent of choice in the treatment of hyponatremic states with water retention, and different studies have demonstrated that they are more effective and practical to use than other traditional approaches in the treatment of diseases such as cirrhosis-related ascites, SIADH and, above all, heart failure. However, the future probably holds the promise of new and unexpected applications for this type of drug in the treatment of several conditions, including polycystic kidney and glomerular disease, glaucoma and Meniere's syndrome.

 

WOW! Cool! I wonder if there are any herbal/supplements that act as aquaretics or vasopressin suppressants that we could try to see if they work???

Evette

 

Hey Cheesie :-*

I am so glad you have bumped this post up cause I was thinking about it a lot this week ???

I have been crook and they "think" I might have SIADH (syndrome of inappropriate antidiuretic hormone) ADH is another name vasopressin ??? ??? It looks like I have it as a side effect of my thiazide diuretics and my SSRI, Efexor. It is apparently a rare side effect of both these drugs. I was all swollen up like a balloon and hardly weeing at all, despite Mazide or Diamox. Basically it means that my ADH or vasopressin was whacked out of normality and told me kidneys to retain water even though I didn't need it My serum sodium was a bit on the low side a few weeks ago when I had blood work done (when this happened before) The oedema never really went away, but it was just minimal and then last week I blew up!!!! LOL (I was back on the Maxide)The chemist thinks this could be the cause, the doc has no idea really but is treating me for it ???

Now, this waterlogged and brain fogged brain can't make head nor tails out of it at the present time and I am trying to link it to the increase in my pressure/fullness since I stopped the Mazide (and am weaning the effexor) am now on Lasix, a loop diuretic instead.....I have put out enough wee in the past few days to fill Sydney Harbour (well, just a bit anyway...LOL) Scary part is that once the Lasix has worn off, I still don't wee enough and I don't want to be on this drug too long, but I still have oedema, just not as bad as it was....I can now see my ankle bones again, but my toes and feet are still podgy....LOL

I am really interested in these aquaretics, they sure sound much better for the bod than Lasix (it can cause major electrolyte imbalances) I will be researching your links even more so now mate ;D ;D Thanks again for the info

Maggie

 

AARRGGGHHHH it won't let me open it....I will try another way but just an after thought....do they name any of the drugs used as Aquaretics ??? ???

 

Hiya Magz.

Sorry about the late reply. Been away for a couple of days.

Damn about the side effects your getting ......I had no idea that a diuretic could mess your ADH like that..... And yup you're right, ADH is just another term for vasopressin. I personally think some of us with meniere's already have a compromised ADH system, so it doesn't surprise me that a meniere's sufferer could suffer from this 'exotic' side effect.

I really don't know much about the availability of these aquaretics .......I had never even heard the term 'aquaretic' until I just read that hyponatremia article. All I knew was that japanese scientists were testing a drug called (OPC-31260) that influences vasopressin and the aquaporin-2 system ......

I just found out though that this (OPC-31260) is actually an Aquaretic ....So atleast I know what to look for now when finding out about it.

Check out this link if you like ...It's pretty interesting

The effects of V2 antagonist (OPC-31260) on endolymphatic hydrops.
"These results indicate that water homeostasis in the inner ear is regulated via the vasopressin-AQP2 system, and that the vasopressin type-2 antagonist OPC-31260 is a promising drug in the treatment of Meniere's disease.

Prof Gibson was telling me that he has been trying to get his hands on this drug, but he says he has had little success. Sounds really great though.

And I definitely think these aquaretics would be perfect for swollen legs and ankles like you've got, because they cut down the bodies ability to absorb water, instead of just trying to turbo charge the urine process like diuretics do.

 

Another thing mags ...Something else that can really throw out your ADH levels is nausea.

Feeling nauseous sends the vasopressin into overdrive. Your body doesn't want to start losing too much good stuff if you start to spew. I'm not sure if you've been feeling off lately though, but it may be contributing.

I think it's a real vicious circle for meneire's sufferers. With shyte ears brings the nausea, but with the nausea brings further fluid retention. So I really think things like VRT are great, because if you can control the chronic nausea to an extent, you might be able to cut out a lot of un-needed ADH from the body.

 

And another thing Maggie lol..

Fred from this forum told me that alcohol helps reduce ADH, so go buy a carton and get on the cans ;D ......being pizzed and swollen might be more enjoyable than just plain old swollen

 

LMAO Cheesie Pissed and swollen would certainly more enjoyable.....I have a drink nearly every night (wine or a G&T) but not enough to get pissed....maybe I should increase the amount I am having and see if the oedema improves ;D ;D

That is certainly one interesting link....I have tried to research the aquaretics but the only ones listed as such are lithium (yes the stuff they use for bi-polar disorder) and demeclocycline (a tetracycline antibiotic) and both of those drugs have mucho side effects so I don't think I want to go that route. One thing I don't need is another toxic drug I wonder if the OPC-31260 is from one of these drugs, but just the part with the vasopressin antagonist ??? Now that would be ideal

I hadn't heard about the nausea link to ADH levels (despite all the bloody research I have done) so thanks for that one.....I have been having constant BAD nausea and dry retching for weeks, but then again I have nausea most of the time, just not as bad as it has been.....first off I was blaming the extra weight, then the oedema, then the Diamox, but it hasn't improved on the lasix, so now I am blaming that ;D My MM/AIED symptoms (and not just during an an attack) have always made me nauseated, all the "extra" movement I get seems to cause it, and this has been going on for years, so it is certainly something to ponder on. Nausea and I are old buddies I still do some of the VRT exercises on a regular basis, mainly the head movement ones, they still make me sick (nauseated and dizzy) and I can't cope without my itsy bittsy dose of valium. I am only on 2mg daily but without it I just can't seem to function....by the arvo I am as crook as Rookwood without it and usually in bed...with it I am just a bit crook, upright and functioning somewhat, but I can cope with that.

I'm off to the docs tomorrow so will update ya on anything new...I don't want to stay on the lasix (it is doing squat for the ear pressure and that is my main worry) but I don't want to go back on the Maxide or Diamox either...not sure what choice I have ??? ??? I can't spend my life all oedematous so am hoping that by stopping the Maxide and weaning off the efexor the SIADH will go away and I can them maybe try something else. My poor kidneys are complaining and its a bit scary that unless i have some sort of diuretic I just don't seem to wee enough....just hoping here that I don't go into kidney failure down the tract a bit

Thanks for your help and tell Prof Gibson if he needs a guinea pig for that AVP antagonist I'm ready and willing (I think ;D ;D)

Love Maggie

 

aww maggie....

Sounds like you're getting hammered from all angles. Not good at all.

Have you tried Moduretic?? ......I know that's the diuretic ol' prof prescribes. Maybe it's worth a try. He prescribed it to me in the 50mg/5mg version when I 1st saw him. I'm hopeless on diuretics though and couldn't handle the postural problems.

I found out about nausea and ADH when I was reading about hyponatremia. Here's the wiki link http://en.wikipedia.org/wiki/Hyponatremia

"Since nausea is, itself, a stimulus for the release of ADH (the antidiuretic hormone, which promotes the retention of water), the potential for a vicious circle of hyponatremia and its symptoms exists."

It's interesting about the lithium isn't it. I actually read a fair bit about when I 1st started looking into all this. I didn't know of demeclocycline though ....might look into that one. So yeah, maybe the opc drug is a derivative of one of these

 

BINGO!!!!

The drug is called Tolvaptan .....Well tolvaptan is actually OPC 41061 ...but OPC 31026 is its parent drug

It isn't released yet, but phase 3 double blind trials are under way in the treatment of polycystic kidney disease. So if these trials continue to go well, it may be released fairly soon. Basically it's getting fast tracked for FDA approval.

 

Excellent article. The "elusive affliction" continues to add more and more plausible causes to a long list.

 

Interesting...however when the doctor did my MRI and other tests, he said my kidney function was better than his...soooo, I don't know if this info is valid. If it is, where would one get that harmone? Blessings, Twinkle

 

just to clear it up

It doesn't mean that people with meniere's have kidney disfunction

It just means that the way inner ear cells hold fluid is very similar manner to the way the kidney holds fluid.

Modern drugs that are soon to be available that work on correcting this problem in the kidney, should also be able to influence the problem in the inner ear due to their similarities.

 

Hey Cheese, this all sounds so very exciting. How many more years of trialling this drug is required before it will be released? My doc has put me on Frusemide which is quite a powerful diuretic but my body seems to be quite used to it now...endured many a trip to the loo - lol! And I'm not too sure it's really doing anything.

You'll keep us informed as to whether your doc gets his hands on this drug and trials it won't you.

 

Very interesting...thanks for the info!

 

Here's a bit more info on the drug Tolvaptan, that is close to gaining FDA approval (though not for mm)

Sorry if it's complex and confusing. It sounds alot more kinder than regular diuretics, as electrolyte imbalance, and postural hypertension are not side effects of these aquaretics.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17445084&query_hl=2&itool=pubmed_docsum

Tolvaptan is an orally effective nonpeptide arginine vasopressin (AVP) V(2)-receptor antagonist synthesized by Otsuka Pharmaceutical Co., Ltd. In in vitro receptor-binding studies, tolvaptan blocked the binding of [(3)H]AVP to human V(2) receptors with 29-fold greater selectivity than that for V(1a) receptors, and showed no inhibition of V(1b) receptors. Tolvaptan inhibited not only the binding of [(3)H]AVP but also the AVP-induced production of cyclic AMP in human V(2)-receptor-expressing HeLa cells. In addition, tolvaptan has no intrinsic V(2) receptor agonistic effect. In in vivo studies, tolvaptan showed marked aquaresis in healthy and diseased animals. In rat models with acute and chronic hyponatremia, tolvaptan improved hyponatremia, resulting in the prevention of death, and improved organ water retention. Tolvaptan reduced cardiac preload without unfavorable effects on renal functions, systemic hemodynamics, or circulating neurohormones in dogs with heart failure (HF). Furthermore, in animal models of human polycystic kidney disease (PKD), tolvaptan showed a decrease in kidney weight as well as in cyst and fibrosis volume. In clinical trials including the "ACTIV in CHF" study, tolvaptan in addition to standard therapy increased fluid loss resulting in decreased body weight, and improved edema and serum sodium without affecting blood pressure, heart rate, or renal functions in patients with HF. In patients with hyponatremia, treatment with tolvaptan without fluid restriction appeared to be more effective than fluid restriction alone at correcting hyponatremia without an increase in adverse events. A phase III trial EVEREST is currently being conducted to evaluate the long-term efficacy and safety of tolvaptan in hospitalized patients with severe HF. In conclusion, tolvaptan offers the possibility of a useful therapy in hyponatremia, congestive heart failure, and various other diseases that are associated with volume overload. Furthermore, tolvaptan is also expected to be effective in the treatment of PKD.

 

Some new stuff

Functional significance of channels and transporters expressed in the inner ear and the kidney.

Quote: "Thus, defects of channels and transporters expressed in the kidney and the inner ear result in simultaneous dysfunctions of these seemingly unrelated organs."

 

Hi Cheese,

I've done some reading in the past on the vasopressin link to hydrops.. I have a tough time understanding all of the medical terms too. It is my understanding that there is research in developing a new line of diuretics that actually control the release of vasopressin, in fact I think that there is a drug out there right now that they are prescribing to diabetics that controls vasopressin. Does anyone have any info on this?

Also, what is cAMP?

Tim M
Johntown, PA

 

Cheese,

Your research is phenominal!!!

I've done some reading on this myself...Did not find nearly the info that you have found. I have a very strong feeling that my hydrops is related to the imbalance of vasopressin. A quick question on the nausea, I have had bad diahrrea on and off for several months now. Do you think your body would react the same for diahrrea as it does for nausea?

Also, when do you think that Tolvaptan will be on the market and is there anyway of getting on a trial of this drug?

Thanks again Cheese, I really think that this may be the answer for a lot of MM sufferers.

Please keep us posted on this one.

Tim M
Johnstown, PA

 

Hey Cheese,

I've been doing some more reading on this and found that Tolvaptan is currently being used in clinical studies in patients with congestive heart failure. When do you think they will get to inner ear problems?

Tim M