title: Levodopa-induced dyskinesias in patients with Parkinson's disease: filling the bench-to-bedside gap.
abstract: Levodopa is the most effective drug for the treatment of Parkinson's disease. However, the long-term use of this dopamine precursor is complicated by highly disabling fluctuations and dyskinesias. Although preclinical and clinical findings suggest pulsatile stimulation of striatal postsynaptic receptors as a key mechanism underlying levodopa-induced dyskinesias, their pathogenesis is still unclear. In recent years, evidence from animal models of Parkinson's disease has provided important information to understand the effect of specific receptor and post-receptor molecular mechanisms underlying the development of dyskinetic movements. Recent preclinical and clinical data from promising lines of research focus on the differential role of presynaptic versus postsynaptic mechanisms, dopamine receptor subtypes, ionotropic and metabotropic glutamate receptors, and non-dopaminergic neurotransmitter systems in the pathophysiology of levodopa-induced dyskinesias.
authors.affiliation: Clinica Neurologica, Università degli Studi di Perugia, Ospedale Santa Maria della Misericordia, Perugia, Italy. calabre@unipg.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabresi
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Di Filippo
authors.forename: Veronica
authors.initials: V
authors.lastname: Ghiglieri
authors.forename: Nicola
authors.initials: N
authors.lastname: Tambasco
authors.forename: Barbara
authors.initials: B
authors.lastname: Picconi
mesh_terms: D000818:Animals; D004409:Dyskinesia, Drug-Induced / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism
chemical_list: D011954:Receptors, Dopamine; D007980:Levodopa