Co-operative binding assay for the characterization of mGlu4 allosteric modulators

Neuropharmacology. 2015 Oct:97:142-8. doi: 10.1016/j.neuropharm.2015.05.017. Epub 2015 May 27.

Abstract

The interest in the role of metabotropic glutamate receptor 4 (mGlu4) in CNS related disorders has increased the need for methods to investigate the binding of allosteric drug candidates. Our aim is to present the first fully characterized in vitro binding assay of mGlu4 positive allosteric modulators (PAMs). Results suggest that mGlu4 PAMs have characteristic co-operative binding with orthosteric glutamate, which offers a notable insight to the further development of mGlu4 targeted therapies.

Keywords: Binding affinity; Metabotropic glutamate receptor; Parkinson disease; mGlu(4).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Regulation
  • Animals
  • Binding, Competitive
  • CHO Cells
  • Cricetulus
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical / methods*
  • Excitatory Amino Acid Agents / chemical synthesis
  • Excitatory Amino Acid Agents / chemistry
  • Excitatory Amino Acid Agents / pharmacology*
  • Glutamic Acid / metabolism
  • Receptors, Metabotropic Glutamate / metabolism*

Substances

  • Excitatory Amino Acid Agents
  • Receptors, Metabotropic Glutamate
  • Glutamic Acid
  • metabotropic glutamate receptor 4