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

摘要

The present invention relates to the chronic treatment with L,3-4-dihydroxyphenylalanine (L-DOPA). Chronic L-DOPA administration still represents the most effective pharmacological therapy of Parkinson's disease (PD) although it is invariably associated with the appearance (within 5-10 years after start of the therapy, 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 dyskinesias (peak dose and diphasic dyskinesias, dystonia). We report for the first time that in an animal model of dyskinesias, administration of agonists at nociceptin/orphanin FQ receptors, termed NOP receptors, dramatically reduces abnormal involuntary movements induced by L-DOPA administration. NOP receptor agonists thus represent a novel class of drugs useful for the treatment of L-DOPA induced dyskinesias.