The first metabotropic glutamate receptor (GPCR-C) was cloned in 1991 (mGluR1). Since then, eight different genes encoding for mGlu receptors have been identified[1]. They can be divided into 3 groups, based on there coupling to the second messenger system of G-proteins: group I is coupled to Gq proteins (mGlu1 and mGlu5), group II (mGlu2 and mGlu3) and group III (mGlu4 mGlu6, mGlu7, and mGlu8) are both coupled to Gi proteins (the latter in recombinant systems), yet are activated primarily by different ligands (2R,4R-aminopiperidindicarboxylic acid and 2-amino-4-phosphonobutyrate respectively). Besides the metabotropic glutamate receptors, ionotropic glutamate receptors do exist as well. The receptors are named after a potent agonist for each receptor subtype (NMDA or N-methyl-D-aspartate, AMPA or alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid, and kainate). Both metabotropic and ionotropic glutamate receptors show the ability to modulate the synaptic plasticity/strength in response to activity which seems a fundamental property of the nervous system and may be an essential component of learning and memory[2]. As a result, the malfunctioning of glutamate receptors (often due to excitotoxicity or overstimulation) is often linked to neurodegenerative diseases such as Alzheimer’s, Huntington’s and multiple sclerosis. Besides classical agonists and antagonists of glutamate receptors (binding to a specific binding site), many positive allosteric modulators (PAM) and negative allosteric modulators (NAM, e.g. Axon 1972) have been identified to interact at this type of receptors. These compounds are inactive on their own, but potentiate or attenuate respectively the action of orthosteric (inverse) agonists[3]. Recent advances in the research for treatment of Parkinson’s disease have implied that stimulation of the metabotropic glutamate receptor 4 (mGluR4) represents a promising new approach to the symptomatic treatment of this neurodegenerative disorder. Our recently added PAMs of the mGluR4 (Axon 1830, Axon 1842, and Axon 1845) may contribute to this research.