Recent advances in positive allosteric modulators of metabotropic glutamate receptors.

Positive allosteric modulators of metabotropic glutamate receptors (mGluRs) are the subject of intensive research due to their emerging therapeutic potential for a range of psychiatric and neurological disorders such as pain, anxiety, cognition, Parkinson's disease and schizophrenia. Positive allosteric modulators, which are small molecules capable of enhancing agonist-mediated receptor activity while possessing no intrinsic agonist activity, have recently been described for group I (mGluR1 and mGluR5), group II (mGluR2) and group III (mGluR4) mGluRs. Relative to classical mGluR agonists, these molecules offer improved selectivity versus other mGluRs and chemical tractability, and may reduce the liability of receptor desensitization.