Letter from Stockholm: Dopamine: Carlsson’s Remarkable Chemical

The first speaker at the 18th International Congress of Parkinson’s Disease and Movement Disorders in Stockholm was Swedish Nobel laureate Arvid Carlsson. Carlsson, now in his 90s, eloquently told the story of his groundbreaking research in the 1950s that led to the dopamine theory of Parkinson’s disease. Carlsson recounted how he used the anti-psychotic medication reserpine to paralyze rabbits and how he then unfroze the animals with dopa. The injected dopa, Carlsson reasoned, had passed into the animals’ brains and been converted to dopamine, a substance that he (but few others at the time) believed was a key neurotransmitter. In a lecture at NIH in 1958, Carlsson theorized that a dopamine deficiency might be the neurochemical basis of Parkinson’s disease in human beings. But as Carlsson told the audience, many leading neuroscientists of the day, such as Sir Henry Dale, treated this dopamine hypothesis with skepticism and even disdain.

Carlsson stuck to his guns. History shows that they were wrong and he was right. By 1970 – thanks the efforts of other luminaries like Birkmayer, Hornykiewicz and Cotzias – levodopa had become the gold standard of treatment. 50-years later, L-dopa is still the therapeutic gold standard for relieving Parkinson’s classic motor symptoms (tremor, slowness, stiffness etc), although patients still must endure the unwanted motor complications that develop with extended use. But, maybe not for long. Based on what was said today in Stockholm, L-dopa may be on the verge of a second act. First, Carlsson and others on the podium spoke encouragingly about the capacity for new ways of delivering L-dopa more continuously – e.g. levodopa/carbidopa intestinal gel (LCIG/Duodopa), gastric retention devices (Depomed, Intec), subcutaneous patch pump (Neuroderm) etc – to mitigate motor complications. Second, as neurologist Ray Chaudhuri argued, L-dopa’s benefits don’t seem to be limited to the motor system. The evidence increasingly shows that continuous dopamine replacement technologies like the Duodopa system – invented, incidentally, in Sweden – not only reduce off time and dyskinesias, they also improve some (but not all) non-motor symptoms of Parkinson’s disease, such as anxiety, depression, sleep disorders, pain, urinary and bowel problems, and visual issues.

Science owes Carlsson a great debt of gratitude for what he uncovered about dopamine. It’s remarkable that this simple molecule, once viewed as an insignificant chemical bystander, should turn out to play such a central role in the brain.

The scientific giant left the audience with six words of advice on what to do when your scientific convictions came under attack. “Don’t give in…stick it out.” It all made for a great first day.