Abstract
Metabotropic glutamate receptor 4 (mGlu4) negatively modulates GABA and glutamate release in the 'indirect pathway' of the basal ganglia, and has thus been proposed as a potential target to treat motor symptoms in Parkinson's disease. Here, we present an extensive comparison of the behavioural effects produced by the mGlu4 positive allosteric modulator (PAM), VU0364770, and the mGlu4 orthosteric agonist, LSP1-2111, in rats with unilateral 6-OHDA lesions. The compounds' activity was initially assessed in a test of haloperidol-induced catalepsy in intact rats, and effective doses were then evaluated in the hemiparkinsonian animal model. Neither of the two compounds modified the development of dyskinetic behaviours elicited by chronic treatment with full doses of l-DOPA. When given together with l-DOPA to rats with already established dyskinesias, neither VU0364770 nor LSP1-2111 modified the abnormal involuntary movement scores. VU0364770 potentiated, however, the motor stimulant effect of a subthreshold l-DOPA dose in certain behavioural tests, whereas LSP1-2111 lacked this ability. Taken together, these results indicate that a pharmacological stimulation of mGlu4 lacks intrinsic antidyskinetic activity, but may have DOPA-sparing...Continue Reading
References
Oct 1, 1989·Trends in Neurosciences·R L AlbinJ B Penney
Sep 25, 1997·Journal of Medicinal Chemistry·F C AcherJ P Pin
Mar 28, 1998·British Journal of Pharmacology·M A Wigmore, M G Lacey
Oct 10, 1998·The European Journal of Neuroscience·M A CenciA Björklund
Jun 16, 2004·Behavioural Brain Research·M A DelfinoO S Gershanik
Sep 18, 2004·The British Journal of Surgery·N LabropoulosO Paxinos
Nov 9, 2005·Nature Reviews. Neuroscience·P Jeffrey ConnFerdinando Nicoletti
Apr 3, 2007·Trends in Neurosciences·M Angela Cenci
Jul 31, 2007·Biological Psychiatry·Jenny E WestinM Angela Cenci
Jul 31, 2008·Molecular Pharmacology·Colleen M NiswenderP Jeffrey Conn
Apr 10, 2009·The Journal of Pharmacology and Experimental Therapeutics·Daniella RylanderM Angela Cenci
Jun 13, 2009·Biological Psychiatry·Sanja DarmopilRosario Moratalla
Jun 16, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Corinne BeurrierMarianne Amalric
Aug 26, 2009·CNS & Neurological Disorders Drug Targets·Kari A JohnsonColleen M Niswender
May 11, 2010·Neurobiology of Disease·Daniella RylanderM Angela Cenci
Aug 5, 2010·Proceedings of the National Academy of Sciences of the United States of America·Helen S BateupPaul Greengard
Aug 16, 2011·CNS & Neurological Disorders Drug Targets·M A CenciP Odin
Nov 15, 2011·Progress in Neurobiology·Véronique Sgambato-Faure, Maria Angela Cenci
Apr 3, 2012·Neuroscience·H IderbergE Y Pioli
Apr 12, 2012·Neuropharmacology·Khaled-Ezaheir BennouarPaolo Gubellini
May 29, 2012·Neuropharmacology·James BogenpohlYoland Smith
Oct 18, 2012·Neurobiology of Disease·Ludivine S BregerEmma L Lane
Sep 14, 2013·Experimental Neurology·Hanna IderbergM Angela Cenci
Mar 7, 2014·Proceedings of the National Academy of Sciences of the United States of America·Myriam HeimanPaul Greengard
May 2, 2014·Frontiers in Neurology·Antonio CerasaAldo Quattrone
Jun 6, 2014·ACS Medicinal Chemistry Letters·Manuel CajinaDario Doller
Jun 22, 2014·Parkinsonism & Related Disorders·Olivier RascolBaltazar Gomez-Mancilla
Jan 8, 2015·Frontiers in Neurology·M Angela Cenci
Citations
Dec 9, 2015·Neuroscience Letters·Caroline BouillotLuc Zimmer
Nov 26, 2015·Bioorganic & Medicinal Chemistry Letters·Kun-Eek KilAnna-Liisa Brownell
Oct 2, 2015·Journal of Medicinal Chemistry·Pedro M Garcia-BarrantesCraig W Lindsley
Mar 31, 2016·Neuroscience and Biobehavioral Reviews·Tetsuya AsakawaYing Xia
Apr 9, 2016·Neuropharmacology·Nadhir LitimThérèse Di Paolo
Jul 26, 2015·Progress in Neurobiology·Matthieu F BastideErwan Bézard
Aug 2, 2015·Bioorganic & Medicinal Chemistry Letters·Zhaoda ZhangAnna-Liisa Brownell
May 4, 2016·Neuropharmacology·Valeria BrunoGiuseppe Battaglia
Oct 19, 2016·Neurobiology of Disease·Irene SebastianuttoM Angela Cenci
Jul 28, 2017·Chinese Medical Journal·Juan-Juan Du, Sheng-Di Chen
Jun 21, 2017·Movement Disorders : Official Journal of the Movement Disorder Society·Tanya ChotibutMichael F Salvatore
Feb 2, 2018·Journal of Neural Transmission·Manuela Mellone, Fabrizio Gardoni
Nov 10, 2018·Expert Opinion on Pharmacotherapy·Nataša Dragašević-MiškovićVladimir S Kostić
Apr 12, 2019·Biomolecules·Fabio Del BelloWilma Quaglia
Feb 12, 2019·Medicinal Research Reviews·Youwen Xu, Zizhong Li
Apr 7, 2020·Journal of Parkinson's Disease·Elizabeth MannSusan Duty
Aug 14, 2020·CNS Drugs·Paulina Gonzalez-LatapiSusan H Fox
Sep 11, 2019·International Journal of Molecular Sciences·Zhu ZhangKen Kin-Lam Yung
Feb 26, 2019·Frontiers in Molecular Neuroscience·Rosalia CrupiSalvatore Cuzzocrea
Dec 29, 2020·Pharmacological Reviews·Karen J Gregory, Cyril Goudet
Oct 20, 2020·Expert Opinion on Investigational Drugs·Dario DollerMikhail Kalinichev
Mar 27, 2018·Neuropharmacology·Delphine Charvin
Apr 6, 2021·The European Journal of Neuroscience·Isabelle WakuAmanda R de Oliveira
Aug 1, 2021·Neurotoxicology·Changqing Zheng, Feng Zhang
May 18, 2021·Journal of Parkinson's Disease·Benjamin VidalLuc Zimmer