Polly - About Balance Issues . . .

[tex]

I've been taking rasagiline, (Azilect in the U.S.), for Parkinson's, for almost 3 months, now. I've been noticing that my balance is improving. Last night, while drying off after taking a bath, I noticed that I can balance on one leg with no problems, now - either leg. I haven't been able to do that in several years. I don't find myself bumping against things, nearly as often, as I did before. I never noticed that I was depressed, before, but I do notice that my mood is better now, and my spirits are noticeably higher, etc. I can't tell if I'm "smarter" now, but my reflexes are better, so I have to say that this stuff certainly seems to work. The only downside, so far, is that I seem to dream most of the time while I'm sleeping - no nightmares, just realistic, true-to-life dreams about everyday experiences, except that they're original - IOW, they're not repeats of daily experiences, but rather new material.

I was doing a little reading about rasagiline, and apparently the fellow who developed the product, a college professor in Israel, is interested in trying to find ways to defeat the ageing process, and this product, and one or two others that he's working on, fit into that overall plan. Now, I recall that you've been sort of interested in the research going on to try to break through the apparent genetic potential life-time "ceiling", at around 115 years of age. The site where I was reading about rasagiline, seems to be focused on extending life expectancies, and reducing health issues that interfere with reaching that goal. I found these quotes to be interesting:

A slowing down of mental processes is sometimes mistaken for dementia; but as a rule of thumb, "if you give a Parkinson's patient time to answer a question, they will answer. If you give an Alzheimer's patient time to answer a question, they will forget the question".

Some 50% of Parkinsonians become clinically depressed; there is accumulating evidence that the depressive symptoms of "dopamine deficiency disorder" are directly tied to the neuroanatomical degeneration.

Hey - I'm a Parkinsonian! How about that? It sounds kinda impressive, when you put it that way.

Anyway, some authorities believe that we will all eventually get Parkinson's disease, if we live long enough, (referring to the goal to extend life expectancies far past 115 year "ceiling". Parkinson's symptoms begin to become apparent, after about 80% of the dopamine neurons have been lost. Just thinking out loud here - perhaps this loss of dopamine begins the day we are born. What if we initiated a program to slow down the loss of dopamine, decades before it is likely to reach the 80% level. Apparently these guys are thinking along those lines.

For rasagiline (modestly) improves cognitive performance on a range of tests, suggesting a role in improved central cholinergic function that is still obscure. More speculatively, a low-dosage regimen of rasagiline may prevent or retard the onset of Parkinsonian symptoms, dementia and diminished vitality in the wider, notionally healthy community as a whole. Such usage is likely to remain off-label for the foreseeable future.

Apoptosis is an active process of programmed cell-death induced by exposure to neurotoxins. Rasagiline and other propargylamines can rescue deteriorating dopaminergic neurons by inhibiting the "death signal" transduction-mechanism of mitochondrial permeability transition.

Chronic rasagiline use increases the activity of the antioxidative enzymes superoxide dismutase (SOD) and catalase (CAT), both in the dopaminergic systems of the brain and also in the heart and kidneys. Professor Youdim speculates that one day rasagiline will be used not just as a prophylactic against neurodegenerative disease but as a cardioprotectant.

This is getting interesting, isn't it.

Selegiline, (mentioned in the next quote), is a predecessor of rasagiline.

The effects of a long-term regimen of rasagiline on human life-expectancy and maximum lifespan are unknown. Yet since low-dosage selegiline can increase both life-expectancy and maximum lifespan in a number of non-human animal species, it is possible, though again unproven, that rasagiline's superior metabolic profile may offer advantages for life-extension. The only other current routes to enhanced longevity are either caloric restriction (CR) - which takes brutal self-discipline and can compromise mood, virility and vitality - or, hypothetically, the use of compounds like resveratrol which mimic the effects of caloric restriction without provoking its troublesome side-effects. But they remain clinically unproven too.

About another product that he's working on:

If rasagiline is good news, then other pharmaceutical products on the commercial horizon are better. Perhaps most notable is the neuroprotectant ladostigil (TV3326), again designed by the redoubtable Professor Youdim. Ladostigil inhibits both cholinesterase and MAO activity, enhancing cognitive function and mood alike. Ladostigil is cunningly designed with a propargyl group for MAO inhibition and a carbamate moiety to inhibit cholinesterase. Both the MAO type A and MAO type B inhibition of ladostigil are relatively selective to the brain: liver and small intestine enzymes are less affected.

This advance is important for several reasons. One reason is obviously the plight of a rapidly growing population of elderly Parkinsonian and Alzheimer's patients in need of more effective drug therapies with fewer risks and adverse side-effects. But the potential range of therapeutic application is broader. Most people would like to feel happier, smarter, younger and sexier. Sadly, contemporary antidepressants and nootropics are badly flawed. It's not just that they are often ineffective. They either have anticholinergic "dumb drug" effects like the older tricyclics, or they flatten emotions and kill libido, like the SSRIs. Older unselective, irreversible MAOIs like tranylcypromine (Parnate) and phenelzine (Nardil) can elevate mood, but their risks and accompanying dietary restrictions make them unattractive even for the clinically depressed and their wary physicians. Meanwhile classic nootropic agents such as cholinergic boosters are liable to subdue mood and cause behavioural inhibition. The attraction of dual action agents like ladostigil, on the other hand, is that they promise to lift mood and intellectual performance alike, while offering a measure of protection against the ravages of ageing.

All these quotes came from this article:

http://www.rasagiline.com/

I thought this was an interesting glimpse into this individuals views of what the future might hold, (disclaimer - be aware that it proposes that genetic engineering will become so common that even kids will play around with it):

http://www.paradise-engineering.com/bio ... index.html

Here's another interesting article from that website:

http://biopsychiatry.com/misc/longevitydrug.html

Okay, here's my point: Rasagaline appears to be a safe medication, (where have we heard that line before? ). I'm guessing that your balance issues might be controlled by rasagaline, with the added bonus that it improves memory, cognitive abilities, etc. If you're interested in minimizing some of the primary problems associated with the ageing process, by preventing them from happening, you might want to investigate this product. I think it's the best thing out there, at the moment. It has the least risk of side effects, by far, of any of the neurological treatments, and it appears to be the most effective, (for preventative purposes). Just thinking out loud, again.

Love,
Tex

[Rosie]

Tex, it's wonderful that Resagaline is helping you, but I have to take issue with the following quote:

Apoptosis is an active process of programmed cell-death induced by exposure to neurotoxins. Rasagiline and other propargylamines can rescue deteriorating dopaminergic neurons by inhibiting the "death signal" transduction-mechanism of mitochondrial permeability transition.

I'm a scientist, and have done research involving apoptosis. The quote might leave you with the impression that neurotoxins are the major target of apoptosis, but apoptosis has a number of other extermely important functions in the body that no doubt would also be affected by Resagaline. I'd be most concerned about an icreased risk of cancer, as apoptosis is the major defense of the body against cells with damaged DNA being able to reproduce. All cancers find some way to inactivate apotosis......there are a number of points in the pathway where this can happen. Also, apoptosis is an important in the bodies defense against viruses and also in preventing autoimmunity. So I would be wary about giving Resagaline to young persons with the idea that it would prevent mental deterioration as they get older. I'd want to know more about these side affects over a long period of time, and the dosage issues. Of course we all have to die of something, and perhaps the choice between cancer or dementia is not a hard one to make.........

Rosie

[tex]

Hi Rosie,

Since apoptosis is programmed cell death, and it's an essential part of healing and maintenance of the cells that comprise all of the body's systems, I can certainly understand your concern. The cells comprising the epithelia of the stomach, for example, are replaced on a weekly basis, because they have such a tough job to do, during the digestive process.

If I'm reading the research reports correctly, rasagiline does not just go around willy-nilly, curtailing apoptosis anywhere and everywhere in the body. It specifically targets the dopaminergic neurotoxin, N-methyl(R)salsolinol, in dopaminergic SH-SY5Y cells. Obviously, since I'm not a neurologist, I could be misreading this, but I think that's what it's saying. Here's a reference on that.

http://www3.interscience.wiley.com/jour ... 6/abstract

Parkinson's disease, itself, apparently carries an increased risk of skin cancer, but I don't believe that rasagiline has ever been documented to increase that risk over and above what the disease itself induces.

I wouldn't recommend giving stuff like this to kids, either - I was thinking more along the lines of thirty-somethings, and forty-somethings, and not today - at some point in the future, when the mechanisms by which drugs such as this perform, are better understood. We may not need to do this now, but we probably will, in the future, if we intend to live to be 150, 200, or . . . .?

Tex

[Rosie]

Tex, I took a look at the abstract, and they were just looking at the effects of resagaline on neuronal cells. It didn't say anything about its effects on other cells in the body. I reminds me of the studies with antidipressants, and other neurolgic drugs.......the research only looks at a small subset of actions of a drug....... Phamacological research is actually pretty primitive, and pretends to know more than is warranted, but that's how companies make money. If they were honest, they wouldn't sell many drugs.

Rosie

[angy]

Tex I'm glad that drug is working for you...let's hope things will be looking up from here, can we expect your avatar pic to change soon then, a younger tex lol!!! Joking of course...

[tex]

Rosie,

I hear you, and I totally agree with your observations about the drug compamies. Rasagiline is an antidepressant. However, remember that it's a propargylamine, that irreversibly and selectively inhibits monoamine oxidase type B, (MAO-B).

As background information, for anyone else who might be following this thread, there are two isoforms of monoamine oxidase, MAO-A and MAO-B. MAO-A preferentially deaminates serotonin, melatonin, epinephrine and norepinephrine. MAO-B preferentially deaminates phenylethylamine and trace amines. Dopamine is equally deaminated by both types. Studies show that MAO-B can, under some circumstances, create a harmful chemical called MPP+, (1-methyl-4-phenylpyridinium), that in turn creates free radicals. MPP+ is toxic, and it acts by interfering with oxidative phosphorylation in mitochondria, causing depletion of Adenosine-5'-triphosphate, (ATP), and cell death. It also inhibits the synthesis of catecholamines, reduces levels of dopamine and cardiac norepinephrine, and inactivates tyrosine hydroxylase.

The neurotoxin (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), MPTP, is converted in the brain into MPP+ by the enzyme MAO-B, causing Parkinson's disease in primates, by killing certain dopamine-producing neurons in the substantia nigra area of the brain. MPTP is used to study the disease in animals. Injection of MPTP causes rapid onset of Parkinson's disease. Because MPTP itself is not directly harmful, toxic effects of acute MPTP poisoning can be mitigated by the administration of monoamine oxidase inhibitors, (MAOIs), such as selegiline or rasagiline. MAOIs prevent the metabolism of MPTP to MPP+ by inhibiting the action of MAO-B, minimizing toxicity and preventing neural death.

MPP+ has quite selective abilities to cause neuronal death in dopaminergic cells, apparently through a high-affinity uptake process in nerve terminals normally used to reuptake dopamine after it has been released into the synaptic gap. The dopamine transporter moves MPP+ inside the cell. If you want more details, most of the above information can be found at various locations in Wikipedia.

I find it very interesting that the chloride of MPP+ has been used as a herbicide under the trade name cyperquat and is structurally similar to the herbicide paraquat. Paraquat was a commonly used chemical several decades ago. In agriculture, we used it as a "burn down" chemical, to destroy everything growing in a field, prior to, or immediately after planting a field, (IOW, before the planted seeds had time to germinate/emerge.) It would "burn down" any weeds or grass growing on a field, (which would kill annuals, or course, but it had only a temporary effect on perennials, since it had no residual effect), and it had no pre-emergent effect, so that the planted crop was not affected, as long as the application was made before the crop emerged. I would assume that some landscapers may have used the herbicide, also, if any undesirable plants emerged in an area that they had previously prepared for planting, but the weather, (or anything else), prevented them from planting it for a few weeks.

Since MAO-B inhibition reduces the breakdown mainly of dopamine and phenethylamine, there are no dietary restrictions associated with this. (MAO-A inhibition carries with it the serious risk of a hypertensive spike event, if foods containing tyramine are eaten. Two such drugs, selegiline and rasagiline have been approved by the FDA without dietary restrictions, (except in high dosage treatment where they lose their selectivity). IOW, at a dosage rate of under 2mg daily, no diet restrictions are necessary. The recomended daily dose of rasagiline is 1mg daily, or 0.5mg daily, if taken concurrently with levadopa.

I have tested the claims of selectivity, by checking my BP before eating a chunk of aged cheese, (about 2 to 3 ounces - cheese is of course, a source of tyramine), and checking my BP again, every 10 minutes, for a couple of hours afterwards. I did this twice, and the first time, there was a very slight increase, (an insignificant amount), within 20 minutes after eating the cheese. The second time, my BP actually decreased, during the 10- to 30 minute interval, immediately following eating the cheese. So I have to wonder if my response in the first test might have been a placebo effect.

Anyway, the information above is basically why I consider rasagiline to be a very selective, and generally safe, drug, and not likely to globally affect normal, benefical apoptosis, in the rest of the body.

Tex

[tex]

Angy,

I was going to wait a while, before posting an updated avatar, but to give you an idea of how well it's working, here's a picture that I took this morning.







Tex

[Stanz]

Sizzlin', geez, at this rate you'll be dating young chicks soon, Tex. Time to buy a "hot" car.

Glad to hear this medicine is working for you. I know many people diagnosed with Parkinsons who have been so overmedicated that they cannot walk or communicate and were taking multiple drugs that are counterindicated, etc.

[angy]

Wow! That stuff is fast acting ..ship some over to me hehe!!
Nice pic bt the way..

[JLH]

For sure some for me, too. Wonder drug.

[kimpatt]

[barbaranoela]

Way to funny Galahad-----I knew U had to be a handome devil-- heck I am going to get some of that stuff too!! Not to look like U thou --be kinda funny me walking around looking like U and yet still called Barbara--

All kidding aside---am happy that U are feeling better on this stuff---
Barbara

[connie]

Tex,
It's great to hear of your noticeable improvements. I have to say I can't imagine that you have experienced any mental deficiencies from Parkinsons. Your intelligence level seems quite superior.

Reading about your experience gives great confidence as it seems that any of us could face this condition at some time in our lives. It makes me angry that you have to pay the entire monthly cost out of pocket.

I know you have faced many serious health battles. I am grateful that you have risen above all life has handed you and remained determined to make other lives better. I hope you continue to see beneficial effects in your treatment.
One of the fans,
Connie

[angy]

Iknow you have faced many serious health battles. I am grateful that you have risen above all life has handed you and remained determined to make other lives better. I hope you continue to see beneficial effects in your treatment.

I couldnt have said it any better...an angel in disguise is our tex....Always here listening to us giving us his heart and soul... Now that's angel in my book.... Xx
by the way I love my pp tshirt

[tex]

Thanks everyone,

I appreciate your support. I've been pretty fortunate, all my life, in that all my ailments have been treatable. I can't complain - it could be a lot worse. Life is good.

Angy - glad it arrived in good condition. You've got the only one, in all of Scotland. In fact, you've got the only one in all of the UK.

Tex