NOP RECEPTOR AGONISTS FOR THE TREATMENT OF L-DOPA INDUCED DYSKINESIAS

The present invention relates to chronic administration of L,3-4-dihydroxyphenylalanine (L-DOPA). Chronic L-DOPA administration still represents the most effective pharmacological treatment of Parkinson’s disease (PD) although it is invariably associated with the appearance (within 5-10 years in about 80 % of patients) of motor complications that limit its clinical effectiveness and greatly reduce the quality of life of patients (Obeso et al., 2000). These motor complications encompass motor fluctuations (e.g. wearing off and “on-off” fluctuations) and abnormal involuntary movements or dyskinesia (peak dose and diphasic dyskinesia, dystonia). We report for the first time that in an animal model of dyskinesia, administration of agonists at nociceptin/orphanin FQ receptors, termed NOP receptors, dramatically reduces abnormal involuntary movements induced by L-DOPA. NOP receptor agonists thus represent a novel class of drugs useful for the treatment of L-DOPA induced dyskinesia