title: Current treatment and future prospects of dopa-induced dyskinesias.
abstract: Levodopa-induced dyskinesias (LID) are one of the main issues in the management of Parkinson's disease (PD); once these dyskinesias are established treatment becomes difficult, so preventive strategies should be first evaluated. Although levodopa (LD) treatment has recently been related as risk factor for LID, the main strategy to delay LID is to start PD treatment with dopamine agonists, adding LD at low doses. After LID onset, approaches include reducing single LD doses, reducing or discontinuing monoamine oxidase type B/catechol O-methyltransferase (MAO-B/COMT) inhibitors and extended-release (ER) LD. Amantadine represents the best antidyskinetic tool, and ER amantadine is the most promising upcoming antidyskinetic drug. New LD formulations such as IPX-066 (able to provide continuous dopaminergic stimulation) also represent promising new approaches. The involvement of a nondopaminergic system in the pathogenesis of LID suggests that the modulation of glutamate, serotonin and adenosine could have potential as new upcoming drug targets, but the role of such drugs will still need to be confirmed in randomized controlled trials.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Mazzucchi
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Frosini
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: U
authors.initials: U
authors.lastname: Bonuccelli
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. r.ceravolo@med.unipi.it.
authors.forename: R
authors.initials: R
authors.lastname: Ceravolo
mesh_terms: D000547:Amantadine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002230:Carbidopa / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D017410:Practice Guidelines as Topic; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D003692:Delayed-Action Preparations; D004338:Drug Combinations; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; D000547:Amantadine; D002230:Carbidopa
keywords: Dopaminergic modulation; IPX-066; Levodopa-induced dyskinesias; Parkinson's disease