[soccertese]

this is well explained in an article described a little farther down.

and it ain't easy with oral l-dopa and i don't see anyone posting here with advanced pd reporting great results taking only an extended released agonist or the neupro patch, anecdotally have heard the patch is better for some people.

so knowing that fluctuating l-dopa causes biochemical/transcription changes which might have a negative affect for hours/days, i'd say it is worth trying to achieve a consistant l-dopa level. that seems more art than science but duodopa shows that "quality" is more important than "quantity" with l-dopa. think about it, you pump the carbidopa/levodopa into your intestine, not your blood, you on average improve your "on" time and reduce dyskensia. the only difference between duodopa and oral meds is oral has to pass thru the stomach and duodopa doesn't and consistant dosing.

i don't have dyskinesia but i certainly wear off and am way beyond the "honeymoon" stage and am still playing around with doseages of immediate release and controlled release.

so if one has to take 50mg/hr for quality of life, possibly dissolving in ginger ale to speed delivery, then maybe you might have to do that. the 100mgIR/200mgCR combo makes sense since the CR is less than 70% bioavailable and therefore you could be getting 120mg of l-dopa and it takes longer to get into your bloodstream. i've read CR lasts longer if taken with food, i believe it's in the insert.

IMPAX LABS will be getting their l-dopa tablet approved which is supposed to be as good as STALVO, hopefully better because it is a combo of immediate and controlled release l-dopa.
-------------------
http://www.touchbriefings.com/pdf/2264/Mouradian.pdf
here's interesting discussion of duodopa infusion which is given to patients where oral l-dopa just isn't working well, either too much off time and/or dyskinesia.
--------
i found the following observations very interesting:
Abruptly switching back to intermittent
therapy does not revert the patients to their baseline
severity of motor fluctuations. Rather, a relatively
smooth motor response is enjoyed for at least several
more days until the beneficial effect of continuous
therapy eventually dissipates. The latter observation
suggests that continuous therapy had produced
plastic changes in the basal ganglia, which lasted
well beyond the removal of the physiologic
stimulation and re-introduction of intermittent
therapy. The advantages of continuous dopaminergic
therapy in PD can be gained in both early
and advanced disease where fluctuations can be
ameliorated both by stabilising circulating drug levels
and by normalising some of the central
pharmacodynamic alterations attending chronic,
non-physiologic, intermittent stimulation

2. Clinical experience
has shown that L-dopa given to non-parkinsonian
patients produces no dyskinesias in the absence
of nigral neuronal degeneration.

3. With advancing PD, as the number of dopamineproducing
nigral neurons decrease from about 50%
at the onset of symptoms down to about 20% or
less, striatal dopaminoceptive medium spiny
neurons become increasingly exposed to the
fluctuations in plasma and brain levels of L-dopa
and, hence, dopamine. The presence of a normal
complement of nigral dopaminergic neurons in
non-parkinsonian individuals shields the striatum
from oscillating L-dopa levels.

4. With advancing disease, as more and more neurons
disappear and the capacity to store dopamine and
release it tonically is diminished, standard
intermittent oral therapy with anti-parkinsonian
agents with a relatively short half-life, such as Ldopa,
result in oscillations in striatal intrasynaptic
dopamine levels that mirror the oscillations in
plasma. A neurotransmitter system that is designed
to function normally tonically is replaced with an
artificially pulsatile system. This non-physiologic
situation is believed to underlie the altered
pharmacodynamics of the L-dopa response.
Biochemical and molecular aberrations have been
documented in experimental models as a result of
intermittent stimulation of the nigrostriatal
dopaminergic system.

5. drug delivery such as with intravenous infusion of Ldopa.
Abruptly switching back to intermittent
therapy does not revert the patients to their baseline
severity of motor fluctuations. Rather, a relatively
smooth motor response is enjoyed for at least several
more days until the beneficial effect of continuous
therapy eventually dissipates. The latter observation
suggests that continuous therapy had produced
plastic changes in the basal ganglia, which lasted
well beyond the removal of the physiologic
stimulation and re-introduction of intermittent
therapy. The advantages of continuous dopaminergic
therapy in PD can be gained in both early
and advanced disease where fluctuations can be
ameliorated both by stabilising circulating drug levels
and by normalising some of the central
pharmacodynamic alterations attending chronic,
non-physiologic, intermittent stimulation

[reverett123]

For me, at least, using a short schedule (2 hours) approximates a continuous delivery rate. It is relatively easy to keep track and you just need to remember whether your first dose fell on an even number or odd. If I do mess up, it is fairly easy to merge back into a similar interval since I am never more than one hour off. I think this approach over the last few years has helped me get free of freezng problems and to minimize dykenesias.

[lurkingforacure]

I think I've posted before that we too are on a two-hour med schedule and although every neuro we've told has been amazed that we can maintain this schedule, they have also said that it is much better as (1) you aren't dumping too much into your system at a time, thus the "peak and valley" you see with larger doses does not happen to as large a degree and (2) you are maintaining a fairly steady level of dopamine in the system. The problem, of course, is at night, when we try not to take any meds and that is getting increasingly harder.

This article is interesting to me for another reason: drug holidays. I have read several places that getting off of sinemet resets you to baseline (if you survive, there is that pesky mortality risk), so that even if you were taking 1000mg before, after a short drug holiday, you may start back to 2-300mg and have just as much response as you did years earlier when you first started taking the drug. This is fascinating to me, that in such a short period, the neurons can be "desensitized", I think they call it.

There was also an article I read recently that talked about the theory that most PWP are taking way more drugs than really needed, and how much better they did if they gradually titrated down. Specifically, ldopa. I'll try to find it again but think it was on a parkinson's recovery site.

Thanks for sharing the fruits of your research efforts

[soccertese]

Originally Posted by lurkingforacure

I think I've posted before that we too are on a two-hour med schedule and although every neuro we've told has been amazed that we can maintain this schedule, they have also said that it is much better as (1) you aren't dumping too much into your system at a time, thus the "peak and valley" you see with larger doses does not happen to as large a degree and (2) you are maintaining a fairly steady level of dopamine in the system. The problem, of course, is at night, when we try not to take any meds and that is getting increasingly harder.

This article is interesting to me for another reason: drug holidays. I have read several places that getting off of sinemet resets you to baseline (if you survive, there is that pesky mortality risk), so that even if you were taking 1000mg before, after a short drug holiday, you may start back to 2-300mg and have just as much response as you did years earlier when you first started taking the drug. This is fascinating to me, that in such a short period, the neurons can be "desensitized", I think they call it.

There was also an article I read recently that talked about the theory that most PWP are taking way more drugs than really needed, and how much better they did if they gradually titrated down. Specifically, ldopa. I'll try to find it again but think it was on a parkinson's recovery site.

Thanks for sharing the fruits of your research efforts

it's interesting that with duodopa you don't decrease your l-dopa, you might actually increase it which is pretty surprising since i assume that since it is infused directly into the small intestine more gets into the blood and thus past the BBB. and it appears to be effective for at least 2 years.
http://www.touchbriefings.com/pdf/3009/Mouradian.pdf
i think one has to be very careful when mentioning a drug holiday.

[madamlash]

I am supposed to take 1.5 Carbi/Lev 25-100 every two hours. I find that if I take 1/2 every hour it works considerably better. The problem is trying to remember to take it every hour.

[Atma Namaste]

Originally Posted by reverett123

For me, at least, using a short schedule (2 hours) approximates a continuous delivery rate. It is relatively easy to keep track and you just need to remember whether your first dose fell on an even number or odd. If I do mess up, it is fairly easy to merge back into a similar interval since I am never more than one hour off. I think this approach over the last few years has helped me get free of freezng problems and to minimize dykenesias.

Do you take a pill every two hours, 24/7?

[Atma Namaste]

Originally Posted by soccertese

this is well explained in an article described a little farther down.

and it ain't easy with oral l-dopa and i don't see anyone posting here with advanced pd reporting great results taking only an extended released agonist or the neupro patch, anecdotally have heard the patch is better for some people.

so knowing that fluctuating l-dopa causes biochemical/transcription changes which might have a negative affect for hours/days, i'd say it is worth trying to achieve a consistant l-dopa level. that seems more art than science but duodopa shows that "quality" is more important than "quantity" with l-dopa. think about it, you pump the carbidopa/levodopa into your intestine, not your blood, you on average improve your "on" time and reduce dyskensia. the only difference between duodopa and oral meds is oral has to pass thru the stomach and duodopa doesn't and consistant dosing.

i don't have dyskinesia but i certainly wear off and am way beyond the "honeymoon" stage and am still playing around with doseages of immediate release and controlled release.

so if one has to take 50mg/hr for quality of life, possibly dissolving in ginger ale to speed delivery, then maybe you might have to do that. the 100mgIR/200mgCR combo makes sense since the CR is less than 70% bioavailable and therefore you could be getting 120mg of l-dopa and it takes longer to get into your bloodstream. i've read CR lasts longer if taken with food, i believe it's in the insert.

IMPAX LABS will be getting their l-dopa tablet approved which is supposed to be as good as STALVO, hopefully better because it is a combo of immediate and controlled release l-dopa.
-------------------
http://www.touchbriefings.com/pdf/2264/Mouradian.pdf
here's interesting discussion of duodopa infusion which is given to patients where oral l-dopa just isn't working well, either too much off time and/or dyskinesia.
--------
i found the following observations very interesting:
Abruptly switching back to intermittent
therapy does not revert the patients to their baseline
severity of motor fluctuations. Rather, a relatively
smooth motor response is enjoyed for at least several
more days until the beneficial effect of continuous
therapy eventually dissipates. The latter observation
suggests that continuous therapy had produced
plastic changes in the basal ganglia, which lasted
well beyond the removal of the physiologic
stimulation and re-introduction of intermittent
therapy. The advantages of continuous dopaminergic
therapy in PD can be gained in both early
and advanced disease where fluctuations can be
ameliorated both by stabilising circulating drug levels
and by normalising some of the central
pharmacodynamic alterations attending chronic,
non-physiologic, intermittent stimulation

2. Clinical experience
has shown that L-dopa given to non-parkinsonian
patients produces no dyskinesias in the absence
of nigral neuronal degeneration.

3. With advancing PD, as the number of dopamineproducing
nigral neurons decrease from about 50%
at the onset of symptoms down to about 20% or
less, striatal dopaminoceptive medium spiny
neurons become increasingly exposed to the
fluctuations in plasma and brain levels of L-dopa
and, hence, dopamine. The presence of a normal
complement of nigral dopaminergic neurons in
non-parkinsonian individuals shields the striatum
from oscillating L-dopa levels.

4. With advancing disease, as more and more neurons
disappear and the capacity to store dopamine and
release it tonically is diminished, standard
intermittent oral therapy with anti-parkinsonian
agents with a relatively short half-life, such as Ldopa,
result in oscillations in striatal intrasynaptic
dopamine levels that mirror the oscillations in
plasma. A neurotransmitter system that is designed
to function normally tonically is replaced with an
artificially pulsatile system. This non-physiologic
situation is believed to underlie the altered
pharmacodynamics of the L-dopa response.
Biochemical and molecular aberrations have been
documented in experimental models as a result of
intermittent stimulation of the nigrostriatal
dopaminergic system.

5. drug delivery such as with intravenous infusion of Ldopa.
Abruptly switching back to intermittent
therapy does not revert the patients to their baseline
severity of motor fluctuations. Rather, a relatively
smooth motor response is enjoyed for at least several
more days until the beneficial effect of continuous
therapy eventually dissipates. The latter observation
suggests that continuous therapy had produced
plastic changes in the basal ganglia, which lasted
well beyond the removal of the physiologic
stimulation and re-introduction of intermittent
therapy. The advantages of continuous dopaminergic
therapy in PD can be gained in both early
and advanced disease where fluctuations can be
ameliorated both by stabilising circulating drug levels
and by normalising some of the central
pharmacodynamic alterations attending chronic,
non-physiologic, intermittent stimulation

For several years I have gone for ~ 15 hours out of 24 between Levo/Carb sessions @100/25 every 2 hours for a total of apx. 600 mg /day, beginning around 5 to 6 a.m. Recently, desperation time has come earlier in the night; last night I only made it to 2:45 a.m. But then I can get a couple hours of sleep until the next one . . . I find it is imperative to have an empty stomach at the beginning of the Levo/Carb day, or one risks not coming "on" with the first pill, a truely miserable experience.

Broken-cell-wall-chlorella, according to a DO I saw recently, is evidently good for cleaning up debris in the brain from Dopamine metabolization, but it is thought to chelate out the drug, decreasing availability. So it seems best to confine it to protien time. Just when the whole scenario seems to stabilize enough to attempt to pin it down with an analysis for possible comparison, it is liable to change.

[Atma Namaste]

Originally Posted by soccertese

this is well explained in an article described a little farther down.

and it ain't easy with oral l-dopa and i don't see anyone posting here with advanced pd reporting great results taking only an extended released agonist or the neupro patch, anecdotally have heard the patch is better for some people.

so knowing that fluctuating l-dopa causes biochemical/transcription changes which might have a negative affect for hours/days, i'd say it is worth trying to achieve a consistant l-dopa level. that seems more art than science but duodopa shows that "quality" is more important than "quantity" with l-dopa. think about it, you pump the carbidopa/levodopa into your intestine, not your blood, you on average improve your "on" time and reduce dyskensia. the only difference between duodopa and oral meds is oral has to pass thru the stomach and duodopa doesn't and consistant dosing.

i don't have dyskinesia but i certainly wear off and am way beyond the "honeymoon" stage and am still playing around with doseages of immediate release and controlled release.

so if one has to take 50mg/hr for quality of life, possibly dissolving in ginger ale to speed delivery, then maybe you might have to do that. the 100mgIR/200mgCR combo makes sense since the CR is less than 70% bioavailable and therefore you could be getting 120mg of l-dopa and it takes longer to get into your bloodstream. i've read CR lasts longer if taken with food, i believe it's in the insert.

IMPAX LABS will be getting their l-dopa tablet approved which is supposed to be as good as STALVO, hopefully better because it is a combo of immediate and controlled release l-dopa.
-------------------
http://www.touchbriefings.com/pdf/2264/Mouradian.pdf
here's interesting discussion of duodopa infusion which is given to patients where oral l-dopa just isn't working well, either too much off time and/or dyskinesia.
--------
i found the following observations very interesting:
Abruptly switching back to intermittent
therapy does not revert the patients to their baseline
severity of motor fluctuations. Rather, a relatively
smooth motor response is enjoyed for at least several
more days until the beneficial effect of continuous
therapy eventually dissipates. The latter observation
suggests that continuous therapy had produced
plastic changes in the basal ganglia, which lasted
well beyond the removal of the physiologic
stimulation and re-introduction of intermittent
therapy. The advantages of continuous dopaminergic
therapy in PD can be gained in both early
and advanced disease where fluctuations can be
ameliorated both by stabilising circulating drug levels
and by normalising some of the central
pharmacodynamic alterations attending chronic,
non-physiologic, intermittent stimulation

2. Clinical experience
has shown that L-dopa given to non-parkinsonian
patients produces no dyskinesias in the absence
of nigral neuronal degeneration.

3. With advancing PD, as the number of dopamineproducing
nigral neurons decrease from about 50%
at the onset of symptoms down to about 20% or
less, striatal dopaminoceptive medium spiny
neurons become increasingly exposed to the
fluctuations in plasma and brain levels of L-dopa
and, hence, dopamine. The presence of a normal
complement of nigral dopaminergic neurons in
non-parkinsonian individuals shields the striatum
from oscillating L-dopa levels.

4. With advancing disease, as more and more neurons
disappear and the capacity to store dopamine and
release it tonically is diminished, standard
intermittent oral therapy with anti-parkinsonian
agents with a relatively short half-life, such as Ldopa,
result in oscillations in striatal intrasynaptic
dopamine levels that mirror the oscillations in
plasma. A neurotransmitter system that is designed
to function normally tonically is replaced with an
artificially pulsatile system. This non-physiologic
situation is believed to underlie the altered
pharmacodynamics of the L-dopa response.
Biochemical and molecular aberrations have been
documented in experimental models as a result of
intermittent stimulation of the nigrostriatal
dopaminergic system.

5. drug delivery such as with intravenous infusion of Ldopa.
Abruptly switching back to intermittent
therapy does not revert the patients to their baseline
severity of motor fluctuations. Rather, a relatively
smooth motor response is enjoyed for at least several
more days until the beneficial effect of continuous
therapy eventually dissipates. The latter observation
suggests that continuous therapy had produced
plastic changes in the basal ganglia, which lasted
well beyond the removal of the physiologic
stimulation and re-introduction of intermittent
therapy. The advantages of continuous dopaminergic
therapy in PD can be gained in both early
and advanced disease where fluctuations can be
ameliorated both by stabilising circulating drug levels
and by normalising some of the central
pharmacodynamic alterations attending chronic,
non-physiologic, intermittent stimulation

For several years I have gone for ~ 15 hours out of 24 between Levo/Carb sessions @100/25 every 2 hours for a total of apx. 600 mg /day, beginning around 5 to 6 a.m. Recently, desperation time has come earlier in the night; last night I only made it to 2:45 a.m. But then I can get a couple hours of sleep until the next one . . . I find it is imperative to have an empty stomach at the beginning of the Levo/Carb day, or one risks not coming "on" with the first pill, a truely miserable experience.

Broken-cell-wall-chlorella, according to a DO I saw recently, is evidently good for cleaning up debris in the brain from Dopamine metabolization, but it is thought to chelate out the drug, decreasing availability. So it seems best to confine it to protien time. Just when the whole scenario seems to stabilize enough to attempt to pin it down with an analysis for possible comparison, it is liable to change.

[reverett123]

Generally speaking, yes. A typical day for me begins at 5:00 AM with a C/L 100/25 plus a C/L 200/50 and, if the bladder has been active in the night, a B-complex and a magnesium-potassium combo. Then at 7:00 AM I am uswually "on" and take another pair of the two forms of C/L along with whatever I am experimenting on. Repeat the pair at 9 AM, 11 AM, 1 PM, 3 PM (plus beta blocker and ACE inhibitor), 5 PM, and 7 PM. May have another at 9 PM but often not.

I know that that sounds like a lot, but I have little trouble with dyskinesia or similar woes and my freezing is seldom a factor. I was taking a heck of a lot of requip before this and jerking like a puppet plus daily freezing. This regimen, especially with the acetyl-l-carnitine, is a piece of cake and doesn't scare my wife so badly. I see danger in the multi-pharmacy approach and seem to be steadily improving.

Originally Posted by Atma Namaste

Do you take a pill every two hours, 24/7?

[Bob Dawson]

[QUOTE=reverett123 (plus beta blocker and ACE inhibitor)

I have great difficulty maintaining a steady-state of almost anything; I can go one hour, or four hours, without drugs; absorption rates seem to vary endlessly, and different levels of emotional uproar or celebration or a hurricane or a good song seem to change the production of l-dopa in my own burnt -out brain, thereby messing up my perfect dosage. I have 2 default positions: very high and very low.

Also, i get up sometimes at midnight; by 9 a.m. my pills for the day are already gone. Doc says take 3 a day at meals; mine are all gone when the sun comes up, so i improvise but not too well. yesterday i went to bed at 4:00 and got up at 10:00. That's p.m. I had breakfast at 11:00 p.m. i try to also sleep a second time in the day -- it's not 24 hour days; i do two 12 hour days, sometimes 4 six-hour days; hard to keep an even keel.

but the reason i am here now is again i saw the R123 statement about ACE inhibitor;. what is it and where i can i get some? Can I smoke it? I want some because R123 has already done the Phase 3 clinical tests... on himself, as usual. And he says that his ACE inhibitor works.
I let Rick test all my drugs before i take any. So does Merck, I hear. If it doesn't kill him, the FDA knows it must be okay. He has survived inhibiting his ACE and i didn't even know we have ACE's to inhibit.
Rick, where's the legal source for ACE apps.?