Novel Glutamatergic Modulators for the Treatment of Mood Disorders: Current Status.
CNS drugs May 1, 2021 Ioline D Henter, Lawrence T Park, Carlos A Zarate
Many patients with mood disorders such as major depressive disorder and bipolar depression do not respond well to standard antidepressants, creating a need for new treatments. Dysfunction in the brain's glutamate system is thought to play a role in these disorders. Subanesthetic doses of racemic (R,S)-ketamine, a glutamatergic modulator, have been observed to produce rapid reductions in depressive symptoms. This has led to investigation of other glutamate-modulating agents, including broad modulators, glycine site modulators, NMDA receptor antagonists, metabotropic glutamate receptor modulators, and mTORC1 activators. Most are in early development and have shown modest effects compared to (R,S)-ketamine and esketamine, though some have more favorable characteristics. The most promising agents appear to be those targeting ionotropic glutamate receptors.