Metabotropic glutamate receptor 4 (mGlu 4)-positive allosteric modulators for the treatment of Parkinson's disease: Historical perspective and review of the patent literature

Craig W. Lindsley, Corey R. Hopkins

Research output: Contribution to journalReview articlepeer-review

28 Scopus citations


Introduction: Metabotropic glutamate receptor 4 (mGlu 4) is a group III GPCR and has been demonstrated to play a major role in a number of therapeutic areas within the CNS. As the orthosteric site of all glutamate receptors is highly conserved, modulating mGlu 4 via allosteric modulation has emerged as a very attractive mode-of-action and has been validated preclinically in a number of animal models for Parkinson's disease, anxiety, pain, and neuroinflammation. Areas covered: In this review, the patent literature for mGlu 4-positive allosteric modulators over the past 4 years will be provided. Patents from all companies are discussed and an overview of the chemical matter and relevant biological properties will be given. Expert opinion: Although there has yet to be an mGlu 4-positive allosteric modulator progressed into clinical trials, there is a wealth of preclinical data from the primary literature that shows the promise of this emerging target. A number of academic and industry laboratories have recently published exciting patent data covering a multitude of chemical matter. Positive allosteric modulation of mGlu 4 remains one of the more attractive non-dopaminergic therapies for Parkinson's disease, as well as emerging data for other indications such as pain, neuroinflammation, schizophrenia and diabetes, which could potentially make mGlu 4 a significant therapeutic target going forward.

Original languageEnglish (US)
Pages (from-to)461-481
Number of pages21
JournalExpert Opinion on Therapeutic Patents
Issue number5
StatePublished - May 2012
Externally publishedYes


  • CNS
  • Metabotropic glutamate receptor 4
  • Non-dopaminergic therapies
  • Parkinson's disease
  • Positive allosteric modulators

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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