Abnormalities of glutamatergic transmission are implicated in neuropsychiatric disorders. Among the glutamate receptors, metabotropic (mGlu) 2/3 receptors have recently gained much attention as molecular targets for the treatment of several neuropsychiatric disorders including depression and anxiety. Both orthosteric and allosteric antagonists of mGlu2/3 receptors have been synthesized, and their therapeutic potential has been examined. These research activities have demonstrated the promise of mGlu2/3 receptor antagonists as potential treatment agents for the above-mentioned neuropsychiatric disorders. In particular, it has been considered that the antidepressant effects of mGlu2/3 receptor antagonists are worthy of pursuing, since the antidepressant profiles as well as synaptic/neural mechanisms involved in the actions of mGlu2/3 receptor antagonists are similar to those of ketamine, which has been demonstrated to show potent, rapid and sustained efficacy in patients with depression, even those resistant to the conventionally prescribed antidepressants. In this chapter, the general pharmacology of mGlu2/3 receptor antagonists and their therapeutic potential are reviewed. In particular, I focus on the usefulness of mGlu2/3 receptor antagonists as novel antidepressants, in comparison with ketamine.
Keywords: AMPA receptor; Antidepressant; Ketamine; Neuroplasticity; mGlu2/3 receptor antagonist.
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