title: Mavoglurant as a treatment for Parkinson's disease.
abstract: BACKGROUND
  A major unresolved issue in the Parkinson's disease (PD) treatment is the development of l-DOPA-induced dyskinesias (LIDs) as a side effect of chronic L-DOPA administration. Currently, LIDs are managed in part by reducing the L-DOPA dose or by the administration of amantadine. However, this treatment is only partially effective. A potential strategy, currently under investigation, is the coadministration of metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulators (NAMs) and L-DOPA; a treatment that results in the improvement of dyskinesia symptoms and that permits reductions in l-DOPA dosage frequency.
  
  
  METHODS
  The authors examine the role of mGluR5 in the pathophysiology of PD and the potential use of mGluR5 NAM as an adjuvant therapy together with a primary treatment with L-DOPA. Specifically, the authors look at the mavoglurant therapy and the evidence presented through preclinical and clinical trials.
  
  
  CONCLUSIONS
  Interaction between mGluR5 NAM and L-DOPA is an area of interest in PD research as concomitant treatment results in the improvement of LID symptoms in humans, thus enhancing the patient's quality of life. However, few months ago, Novartis decided to discontinue clinical trials of mavoglurant for the treatment of LID, due to the lack of efficacy demonstrated in trials NCT01385592 and NCT01491529, although no safety concerns were involved in this decision. Nevertheless, the potential application of mGluR5 antagonists as neuroprotective agents must be considered and further studies are warranted to better investigate their potential.
authors: Universitat de Barcelona, Institut de Biomedicina (IBUB), Centros de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Unitat de Farmacologia I Farmacognòsia, Facultat de Farmàcia , Barcelona, Avda/Joan XXIII , Spain camins@ub.edu.
authors: Dmitry
authors: D
authors: Petrov
authors: Ignacio
authors: I
authors: Pedros
authors: Maria Luisa
authors: ML
authors: de Lemos
authors: Mercè
authors: M
authors: Pallàs
authors: Anna Maria
authors: AM
authors: Canudas
authors: Alberto
authors: A
authors: Lazarowski
authors: Carlos
authors: C
authors: Beas-Zarate
authors: Carme
authors: C
authors: Auladell
authors: Jaume
authors: J
authors: Folch
authors: Antoni
authors: A
authors: Camins
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004409:Dyskinesia, Drug-Induced / Q000209:etiology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D011788:Quality of Life; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors
chemical_list: D000978:Antiparkinson Agents; D007211:Indoles; D064529:Receptor, Metabotropic Glutamate 5; D007980:Levodopa; C581397:mavoglurant
keywords: Parkinson’s disease; l-DOPA; mavoglurant; mlgu5