Levodopa – history and pharmacology

Parkinson’s as I see it: we invested tons of money to investigate dopamine agonists but couldn’t find any better than dopamine (in the form of l-dopa). The only problem is it’s pharmakokinetics. As for neurotoxicity, I still believe that the small doses used nowadays (as compared to earlier decades or in mice) fare quite well.

So we spend some time reviewing the history of levodopa and the basic pharmacology.

Here are some references:


Fahr’s disease

After stumbling over a CT of a slightly parkinsonian woman with typical calcifications, I tried to read up on Fahr’s disease aka striopallidodentate calcinosis. Tried – i.e., unsuccessfully. Here is an article about it. And here is a review, which I cannot download. I did not find a proper entry in my standard textbooks the goes further than to add it to the list of metabolic symptomatic Parkinson syndromes. There are a lot of case reports along the lines “We saw it and then we read up on it”, but nothing really systematic.

Here are the highlights:

  • Require calcifications in the dentate nucleus and the basal ganglia, possibly more.
  • Expect Parkinsonism and ataxia, possibly more.
  • There is a connection to Ca metabolism disorders, in particular hypoparathyroidism and pseudohypothyroidism, possibly also due to the treatment of these disorders.
  • Guess what: there are familial and sporadic forms.
  • Guess what: no proper treatment.

Restless legs syndrome

Triggered by a complex patient with myasthenia, polyneuropathy, RLS, organic psychosis and several more we discuss what is to be known about the restless legs syndrome, using

For me the first source provided a fundamental insight into the pathophysiology of RLS (heightened circadianic dopamine variations with consecutive desensitization of dopamine receptors) that finally explains why dopaminergic medication can lead to augmentation.

I still can’t understand why we use long-acting dopamine agonists rather than short-acting or at least SR L-Dopa to cover symptoms and this pathophysiologic view would support the view.

Another brilliant development is transcranial sonography for imaging of the SN, finding hypoechogenicity – as reported in