Does exercise increase the effectiveness of levodopa?

PwP on levodopa based drugs rely on the levodopa getting into the brain. There it is converted into dopamine and some good can be done. Any levodopa which is converted into dopamine outside of the brain is, at best, wasted.

While the levodopa is outside the brain it is vulnerable to premature conversion. (The carbidopa that usually comes with levodopa is there to reduce the peripheral conversion rate).

The questions are:

Does exercise reduce the time it takes levodopa to get into the brain?
Does exercise lead to higher levels of dopamine in the brain?

Let's hypothesize that the time it takes levodopa in the blood to get into the brain is inversely proportional to the rate at which blood flows through the brain, i.e. higher cerebral blood flow implies less time for the levodopa to get into the brain.

Cerebral blood flow is increased by exercise [1], but in a complicated way, with some regions doing better than others.

Consider two scenarios:

1. Take the levodopa and sit down waiting for it to take effect. There is relatively less blood flow and less levodopa reaches the brain in any period of time. Peripheral conversion is relatively high. The "on" is delayed, and this leads to less movement reducing the amount of levodopa getting into the brain even more.

2. Take the levodopa and exercise - anything that increases cerebral blood flow. More levodopa gets into the brain; the "on" comes sooner and is of a higher quality because there is more dopamine in the brain. This leads to more movement; higher blood flow and more levodopa in the brain.

There is a paper [2] describing a small clinical trial in this area. Reuter et al. report:
"The mean levodopa concentration in plasma at half-maximal motor effect tended to be higher during exercise and indicated that the patients needed a higher levodopa concentration in plasma to achieve the half-maximal motor effect. The maximal levodopa concentration in plasma tended to be higher with exercise. Both trends did not reach statistical significance."

Unfortunately most of this paper is behind a fire wall.

References

[1] "Exercise increases blood flow to locomotor, vestibular, cardiorespiratory and visual regions of the brain in miniature swine"
Michael D. Delp1, R. B. Armstrong1, Donald A. Godfrey2, M. Harold Laughlin3, C. David Ross4 andM. Keith Wilkerson1
Article first published online: 5 AUG 2004
DOI: 10.1111/j.1469-7793.2001.t01-1-00849.x
http://onlinelibrary.wiley.com/doi/1...1-00849.x/full

[2] Reuter, I., Harder, S., Engelhardt, M. and Baas, H. (2000), The effect of exercise on pharmacokinetics and pharmacodynamics of levodopa. Mov. Disord., 15: 862–868. doi: 10.1002/1531-8257(200009)15:5<862::AID-MDS1015>3.0.CO;2-S
http://onlinelibrary.wiley.com/doi/1...O;2-S/abstract

John

Great Questions

This might shed some light on this

When dopamine-deficient mice were given levodopa and run on a special kind of treadmill, their motor performance improved over mice who ran the treadmill without the dopamine drug, or mice who received the drug without exercise. Even after the drug was stopped, the benefits persisted in a manner similar to the long-duration response observed in Parkinson’s patients. That suggested the long duration response might be the result of motor learning and changes in the brain enhanced through the combination of dopamine replacement and exercise.

Human studies revealed similar results:

The reanalysis of the data confirmed their hypothesis: during levodopa treatment, patients improved their performance on the finger-tapping task with both hands, but the dominant hand improved more than the non-dominant hand. For patients in the placebo group that were not given levodopa, finger-tapping performance was unchanged for both hands. The results supported the idea that dopamine and exercise worked together to boost motor learning and control.

“You need the dopamine to take advantage of more activity leading to better performance,” Kang said. “If you didn’t have dopamine, it didn’t happen, or if you didn’t move as much it didn’t happen. So it was clearly a synergistic effect of being more active and having dopamine.”

http://sciencelife.uchospitals.edu/2...or-parkinsons/