Neurobiology of Depression and Psychopharmacology of Esketamine – A Novel Rapid-acting Antidepressant

Posted on: September 14, 2022
Last Updated: December 28, 2022

In this video, Dr Sanil Rege reviews the neurobiology of depression that describes the various converging hypotheses for the pathophysiology of depression and looks at novel mechanisms of action for Esketamine, a rapid-acting antidepressant.

We examine the roles of glutamate, N-methyl-D-aspartate (NMDA) receptors and brain-derived neurotrophic factor (BDNF) with a focus on the mechanism of action of esketamine (Spravato ®), a new rapid-acting antidepressant indicated for treatment-resistant major depressive disorder. Esketamine is believed to act by:

  • Inhibition of the NMDA receptor resulting in GABAergic inhibition with subsequent increased glutamate release and activation of postsynaptic AMPA receptors
  • Subsequent downstream modulation of mTOR, and additional BDNF production
  • Direct stimulation of BDNF production, resulting in rapid action, neurogenesis and neuroplasticity.

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