Recent Progress in the Development of mGluR4 Positive Allosteric Modulators for the Treatment of Parkinson's Disease

Authors: Lindsley, Craig W.; Niswender, Colleen M.; Engers, Darren W.; Hopkins, Corey R.

Source: Current Topics in Medicinal Chemistry, Volume 9, Number 10, July 2009 , pp. 949-963(15)

Publisher: Bentham Science Publishers

Buy & download fulltext article:

Price: $63.10 plus tax (Refund Policy)

Abstract:

This article describes recent advances in the development and biological evaluation of small molecule mGluR4 positive allosteric modulators (PAMs), and, to a lesser extent, orthosteric agonists. Due to its expression in the basal ganglia, the Family 3 GPCR metabotropic glutamate receptor subtype 4 (mGluR4) has recently garnered a great deal of attention as a putative target for the treatment of Parkinson's disease and a variety of other CNS disorders. Until 2008, with the exception of the prototypical mGluR4 PAM (-)-PHCCC, very few small molecule tools existed to probe the role of selective activation of mGluR4. This review will focus on the explosion of novel mGluR4 PAMs reported in the past year and the further preclinical validation of mGluR4 activation as a potentially groundbreaking treatment for Parkinson's disease.

Keywords: Metabotropic; mGluR4; Parkinson's disease; allosteric; positive allosteric modulator; dopamine; PHCCC; glutamate

Document Type: Research article

DOI: http://dx.doi.org/10.2174/156802609789378272

Affiliations: 1: Vanderbilt Program in Drug Discovery, Department of Pharmacology, Vanderbilt Medical Center, Nashville, TN 37232 USA.

Publication date: 2009-07-01