Serotonin for advanced Parkinson's disease

5 February 2008

Most people with Parkinson’s disease use the drug L-DOPA to give relief from the symptoms such as tremors, rigidity and impaired movement associated with the progressive loss of their motor skills. Unfortunately, as Parkinson’s disease progresses, the drug L-DOPA can cause quite significant side effects that counter it's effectiveness.

Paul Greengard from Rockefeller University USA and colleagues in Sweden have determined that serotonin, a neurotransmitter involved in mood regulation, appetite, sexuality and sleep, also plays a crucial role in Parkinson’s disease. Greengard’s team showed that side effects associated with repeated L-DOPA treatment can be blocked by manipulating a specific serotonin receptor. Their findings, point to a new target for developing treatments for this disorder, which is the second most common neuro-degenerative disease after Alzheimer’s disease.

“Our study provides a scientific rationale for developing drugs that act on the serotonin 1B receptor for the treatment of advanced Parkinsonism,” says senior coauthor Per Svenningsson, a visiting professor in Greengard’s lab and a group leader at the Karolinska Institute in Sweden.

Parkinson’s disease is characterized by a progressive degeneration of dopamine-producing neurons, which causes tremors, rigidity and lack of movement control. The neurotransmitter dopamine has several functions in the brain, including the regulation of movement. These dopamine-producing neurons project from the midbrain to an area of the brain called the corpus striatum. Although dopamine signaling is impaired in Parkinson’s patients, serotonin production remains strong. In addition, several serotonin receptors are highly expressed in the striatum and available to modify the action of L-DOPA.

“Blocking the dopamine D1 receptor is not a treatment option for L-DOPA-induced side effects, since it would diminish the therapeutic efficiency of L-DOPA,” says Greengard, who is Vincent Astor Professor and head of the Laboratory of Molecular and Cellular Neuroscience at Rockefeller. “Developing compounds that target the serotonin 1B receptor may offer an alternative approach for treating advanced Parkinson’s disease.”


Resources
Rockefeller University, USA. For treating advanced Parkinson’s, new research points to serotonin. Accessed 8 February 2008