A basic exercise- How long can one stand on one foot? Best out of five attempts. Test during maximum "on" period for the day.

Two days ago I got zero on each foot.
Today I got five on my right foot and six on my left.

This afternoon it is seven seconds on the right and nine seconds on the left. Also, I skipped a pill at 2:00 with seeming impunity.

It has been rughly a month now and I am quite encouraged with the perindopril. I am also a little hacked off that I wasn't taking it from the day of diagnosis.

I am still a work in progress. My days are much more stable with very little OFF time. I have ditched the ropinerol again and am running on 8x sinemet cr, two hours apart, and continue to lower that. I turn over in bed with little trouble. When I waken to Nature's call in the night (roughly every two hours), my legs are much stronger. There is more muscle mass there, too, and the atrophy has been reversed.

The biggest problem is dyskinesia. I am not too surprised since the earlier study indicated dopamine increase.

I pronounce this to be "Good Stuff"!

RLSmi, thank you. It is nice to know someone is watching. Plus I have a question for you in particular. As I recall, you have been taking low dose dextromethorphan at bedtime for several years. My question is, "What prompted you to select that timing?"

I have settled on a similar schedule for the practical reason that for a couple of hours after taking perindopril my symptoms actually worsen. Taking it at bedtime gets around that. But I have to consider the possibility that other factors similar to those that guide you are at work.

Yesterday I experienced zero time either off or frozen. Almost no dyskinesia as well.

Rick; I began using DM as an OTC substitute for low-dose naltrexone. The basis for taking it at bedtime is the theory put forth by Ian Zagon at Penn State that the cells that produce endorphins and their receptors do so in the middle of the night. The brief "spike" of the drug a couple of hours before then apparently stimulates greater production of the endorphins and receptors, with the effect of enhancing regulatory control of the innate immune system (macrophages and microglial cells). Check references in the LDN web page on Zagon's earlier work for more detail.

On the other hand, Hong's work on suppression of inflammation by these morphinan drugs suggests that a specific enzyme in the microglia responsible for producing superoxide and hydrogen peroxide is the target for the drugs, with the enzyme action being inhibited by extremely low concentrations of not only these morphinans but endorphins themselves!

I can't figure out exactly how the two different explanations might be connected, but the bottom line is that low-dose DM or naltrexone seem to work with some people.

This is probably way more information than you wanted this morning, but I seem to have a hard time stopping once I get rolling on this subject!
Robert

Rick; I failed in my first reply to address your question about the possible connection between your apparent better response to perindopril taken at bedtime and DM taken at bedtime. I have no clue as to what the connection might be. Of course there are myriad known diurnal changes in the endocrine system(s), any one (or more) of which could be affected.
Is perindopril an ACE inhibitor (similar to lisinopril)? My impression was that perindopril's antihypertensive effect has to do with calcium ion regulation.
Robert

It is not so much that there is a better response as it is an initial negative effect lasting a couple of hours. I haven't run across the calcium link. One suggested explanation was that angiotensin2 is a pro-inflammatory cytokine and that its suppression is thus beneficial.

A couple of interesting points- There are only two ACEIs that can pass the BBB, captopril and perindopril.

Research indicates that blueberries have something going for them vis-a-vis PD. Blueberries are also a natural ACEI.

And check this one out-

1. J Neurochem. 1999 Jul;73(1):214-9.

Effect of chronic angiotensin-converting enzyme inhibition on striatal dopamine
content in the MPTP-treated mouse.

Jenkins TA, Wong JY, Howells DW, Mendelsohn FA, Chai SY.

Howard Florey Institute of Experimental Physiology and Medicine, University of
Melbourne, Parkville, Victoria, Australia.

We have previously shown that chronic treatment with the angiotensin-converting
enzyme inhibitor perindopril increased striatal dopamine levels by 2.5-fold in
normal Sprague-Dawley rats, possibly via modulation of the striatal opioid or
tachykinin levels. In the present study, we investigated if this effect of
perindopril persists in an animal model of Parkinson's disease, the
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse. C57BL/6 mice
were treated with the neurotoxin (30 mg/kg/day intraperitoneally) for 4 days and
then left for 3 weeks to allow the degeneration of striatal dopaminergic
terminals. At this time, the mice exhibited a 40% decrease in striatal dopamine
content and an accompanying 46% increase in dopamine D2 receptor levels compared
with control untreated mice. The dopamine content returned to control levels, and
the increase in dopamine D2 receptor levels was attenuated in mice treated with
perindopril (5 mg/kg/day orally for 7 days) 2 weeks after the last dose of MPTP.
When the angiotensin-converting enzyme inhibitor was administered (5 mg/kg/day
for 7 days) immediately after the cessation of the MPTP treatment, there was no
reversal of the effect of the neurotoxin in decreasing striatal dopamine content.
Our results demonstrate that perindopril is an effective agent in increasing
striatal dopamine content in an animal model of Parkinson's disease.


PMID: 10386973 [PubMed - indexed for MEDLINE]

Went shopping this morning. As I came out into the bright sunshine, I was briefly blinded and missed the curb. Went careening toward a 3-point landing onto my nose. But my feet managed to catch up with the rest of me and avert disaster. A similar mishap back in the winter cost me seven stitches in the forehead.

Glad to hear your feet caught up with you before you face planted. Ouch!

Perindopril sounds like a sure thing. I guess it faces a lot more research and studies, though.
I wish I had high blood pressure instead of LBL. I'll never be able to benefit from this drug. Last night my blood pressure was 97/59 after becoming short of breath from doing laundry. Heart rate was 75, but in the past had stayed around 60.
The good news is that many PWP may be able to live better lives with this drug.

Thanks for sharing your experience with it, Reverett.

Tonya

The last few days have featured a good bit of dyskinesia. But yesterday I started taking half pills on the same time frame and am seeing big improvement. Probably a rocky road ahead as I walk a tightrope between quiver and catatonic.

But isn't that what I should expect if neurotransmitters are ramping up? I mean 2.5x is an impressive number.