Home
Resources
Publications
Investigation of the Antidyskinetic Site of Action of Metabotropic and Ionotropic Glutamate Receptor Antagonists. Intracerebral Infusions in 6-hydroxydopamine-lesioned Rats With Levodopa-Induced Dyskinesia

Investigation of the Antidyskinetic Site of Action of Metabotropic and Ionotropic Glutamate Receptor Antagonists. Intracerebral Infusions in 6-hydroxydopamine-lesioned Rats With Levodopa-Induced Dyskinesia

Sotirios Maranis, Dimitrios Stamatis, Christos Tsironis, Spiridon Konitsiotis

Eur J Pharmacol. 2012 May 15;683(1-3):71-7.

PMID: 22410193

Abstract:

Long-term levodopa replacement therapy in Parkinson's disease is confounded by abnormal involuntary movements, known as levodopa induced dyskinesia (LID). Dysfunctional glutamatergic neurotransmission has been implicated in the pathogenesis of LID making metabotropic and ionotropic glutamate receptors attractive novel therapeutic targets. The objective of the present study was to investigate the antidyskinetic site of action of different glutamate receptor antagonists in the brain. For that purpose, metabotropic glutamate subtype 5 (3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine hydrochloride, MTEP), NMDA NR2B selective ((aR,bS)-a-(4-Hydroxyphenyl)-b-methyl-4-(phenylmethyl)-1-piperidinepropanol maleate, Ro 25-6981) and AMPA (2,3-Dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium salt, NBQX) receptor antagonists or saline were administered by intracerebral infusion in the caudate-putamen (CPu), the substantia nigra zona reticulata (SNr) or the subthalamic nucleus (STN) of 6-hydroxydopamine-lesioned rats exhibiting LID. Dyskinesia was assessed with the modified version of the rat Abnormal Involuntary Movements scale (AIMS). Ro 25-6981 and to a lesser extent NBQX improved dyskinesia (82% and 19% reduction in AIM score respectively) after infusion in the caudate-putamen. None of the three drugs managed to noticeably reduce AIM score after infusion in the SNr. MTEP was the only drug that produced a reduction in AIM score (48%) when infused in STN. In conclusion, while the striatum proved important in the antidyskinetic action of NMDA and AMPA receptor antagonists, the results of this study highlight also the importance of the metabotropic glutamate receptors that reside in the STN as therapeutic targets in the treatment of LID.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1312991766	Ro 25-6981 maleate salt		1312991-76-6	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: