Dopamine receptors and L-dopa-induced dyskinesia.
In the majority of Parkinson's disease patients, chronic dopamine replacement therapy leads to involuntary aimless movements known as l-dopa-induced dyskinesia. While mechanisms involved in dyskinesia occurrence are still unclear, dopamine receptors undoubtedly have a central role in their pathophysiology. Here we review current knowledge and evidence for their involvement in dyskinesia genesis and manifestation. We propose that an anti-dyskinetic strategy should target the D1/D3 signalling cascade, as targeting D2 receptor signalling seems to inherently convey anti-therapeutic effects deleterious to patients. As more molecular tools are made available, we will better understand the role of each receptor and its associated signalling cascade in Parkinson's disease and L-dopa-induced dyskinesia, hopefully in a way amenable to patients.
Berthet
Amandine
A
Université Victor-Segalen Bordeaux 2, Centre National de la Recherche Scientifique, Bordeaux Institute of Neuroscience, UMR 5227, Bordeaux, France.
Bezard
Erwan
E
D000818:Animals; D018491:Dopamine Agonists / Q000494:pharmacology / Q000627:therapeutic use; D004409:Dyskinesia, Drug-Induced / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D011954:Receptors, Dopamine / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D007980:Levodopa