Pramipexole serum levels versus nausea levels

[Gerret]

Hello All,

The abstract of my question is: Does the hour by hour pramipexole blood serum level affect the concurrent nausea level in pramipexole users?

I used regular pramipexole (Mirapex) from the day my PCP diagnosed me and prescribed it in 2012 until I augmented on it in 2020 at .75mg. I then switched my care to a neurologist and after copious begging he put me on methadone instead. After 3 years of taking 10 mg methadone I became unconvinced that it was still working (based on how incredible my daily kratom & MM intake became) so I decided 6 weeks ago to ween off of it and see what happens. I lowered my dose by 2.5mg each week. First 3 weeks were a cake walk but the last week was a level of hell that I wouldn't wish on my worst enemy. The RLS became out of control day & night. I got so desperate that I dug a 25mg Mirapex out of my ever expanding freezer pharmacy & took it knowing full well that it would make me nauseous as hell.

I continued on Mirapex for the next few days while my Dr. got hold of some Neupro patch samples for me. For the next 2 weeks I went from 1mg patches up to the 4mg patch with zero RLS improvement but ever increasing nausea. Since both me & my Dr. are running out of ideas, we decided earlier this week to try the ER version of pramipexole since my insurance company does cover it. While I am waiting for my pharmacy to get the ER version in stock, I have been emulating it by taking 3 reduced pramipexole doses daily, something I have never tried before. Previously I only took it once daily regardless of dose.

I am finding on my short test that the nausea is greatly reduced by taking 3 doses daily (every 8 hrs) versus once daily. My current theory is that the serum fluctuation of once daily dosing may have contributed my previous nausea.

Since so few of us have any experience with pramipexole ER due to it's cost, I'm curious if anyone has tried 2X or 3X daily dosing with regular pramipexole and if so how did it affect their nausea levels?

Thank You.

[Rustsmith]

First off, I never experienced nausea with pramipexole. However, I can offer a few comments that may help you.

First, our normal dopamine levels vary throughout the day. They are highest when you wake up in the morning and then slowly decline throughout the day and then are lowest when you need to go to bed at night. This is sort of the body's way of controlling your usable energy levels.

Second, the Neupro patch was developed as a time release dopamine agonist (sort of like pramipexole or ropinerole ER). The idea behind it was that by avoiding the spike that your body experiences when taking a dopamine pill (any form) at night, it helps keep your body's dopamine levels more constant. The thought at the time was that this might help avoid augmentation, which it did not.

Unfortunately, Neupro and the ER form of pramipexole and rotigatine are very expensive. Neupro is sometimes covered by insurance but the two ER drugs usually are not.

Finally, after Neupro was developed, researchers realized that the problem isn't low or fluctuating dopamine levels, it is non-functioning dopamine receptors due to low brain iron. Adding more dopamine to the brain via dopamine agonists only forces the remaining dopamine receptors to work harder. As for augmentation, the current thought is that the problem has to do with an imbalance in the types of dopamine receptors that remain working. The body has D1 through D4 receptors. RLS meds tend to be D2 specific and the augmentation theory indicates that the D1 type are working harder due to the high dopamine levels in the brain and spine.