Spravato

Esketamine, the S-enantiomer of racemic ketamine, is an antidepressant with a novel mechanism of action. It is a non-selective, non-competitive, antagonist of the N-methyl-D-aspartate (NMDA) receptor, an ionotropic glutamate receptor. Putative aetiological contributors of depression, including stress and other conditions, are known to cause structural and functional impairment of synapses in brain regions involved with the regulation of mood and emotional behaviour. Evidence within the literature suggests that through NMDA receptor antagonism, esketamine produces a transient increase in glutamate release leading to increases in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) stimulation and subsequently to increases in neurotrophic signalling that restore synaptic function in these brain regions. Unlike other antidepressant therapies, esketamine's primary antidepressant action does not directly involve monoamine, gamma-aminobutyric acid (GABA), or opioid receptors.