jeffreyn,

Thank you. It's an interesting topic.

In my own reading, I have occasionally came across claims of a long term response to levodopa, but I never really bought into them. I have never, knowingly at least, experienced anything that couldn't be explained by the standard pharmacokinetic models, plus dopamine storage in vesicles.

I'm 13 years post diagnosis, and some 15 hours since my last dose, but I still experience good performance in the morning before taking my drugs. When I do get around to taking them, I will start by getting worse, especially my tremor, before they kick in, and the tremor is greatly reduced.

However, the case in favour of the long duration response certainly looks more persuasive when you actively seek out the case for it.

Unfortunately it's behind a paywall, but Anderson and Nutt have written about the long duration resonsponse to levodopa [1]:

"The antiparkinsonian response to levodopa is characterized by an immediate motor improvement lasting hours and a more sustained response lasting days. These two responses have been referred to as the short-duration response (SDR) and the long-duration response (LDR). The LDR represents a substantial component of the clinical effect of levodopa ..."

Unfortunately it's behind a paywall, but Nagao et al. write [2]:

"Over a mean treatment period of 16.6 ± 4.4 years, annual increase in motor disability was 2.3% of the maximum score. The long duration response composed 49% of total levodopa response during the first decade of treatment, and this proportion was significantly higher soon after commencing levodopa (p = 0.001). Higher pre-treatment motor score (r = 0.60) and lower MMSE (r = 0.60) were the main predictors of a larger long duration response. There was little correlation between long and short duration responses."

References:

[1] "The long-duration response to levodopa: Phenomenology, potential mechanisms and clinical implications"
Elise Anderson, John Nutt
Parkinsonism and Related Disorders, Sept 2011
https://www.prd-journal.com/article/...087-3/fulltext

[2] "Inferring the long duration response to levodopa in Parkinson’s disease"
Kanae Nagao et al.
Parkinsonism and Related Disorders, Sept 2018
Inferring the long duration response to levodopa in Parkinson’s disease - ScienceDirect

John