Metabotropic glutamate receptors (mGlu receptors) belong to the G-protein-coupled receptors superfamily. They are divided into three groups, in which group II and group III belong to presynaptic receptors that negatively modulate glutamate and γ-aminobutyric acid (GABA) release when activated. In this review, we introduce not only the functions of mGlu receptors, but also the group II and group III allosteric modulators and agonists/antagonists reported over the past five years according to a classification of their structures, with a specific focus on their biological activity and selectivity. In particular, the structure of these compounds and the future directions of ideal candidates are highlighted.
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