Depression is one of the most common mental disorders and is a leading cause of disability worldwide. It is characterized by intense sadness, loss of interest in usual activities, feelings of helplessness and worthlessness, decreased appetite, loss of energy, and more. It is estimated that over 264 million people worldwide suffer from depression. Some factors contributing to the development of depression include genetic factors, stress, traumatic events, and imbalance of neurotransmitters in the brain (such as adrenaline, noradrenaline, dopamine, glutamate, GABA, and acetylcholine). Neurotransmitters play a role as mediators in signal transmission between neurons by binding to specific receptors. NMDA (N-methyl-d-aspartate) is an excitatory receptor for glutamate. When glutamate binds to the NMDA receptor, nerve signals are transmitted. Richard Morris and John Watkins discovered it, and its discovery was crucial for understanding neurotransmission processes and brain functioning. Research has shown that dysfunction of NMDA receptors is associated with the development and manifestation of depression due to insufficient glutamate neurotransmission. Therefore, some antidepressants target NMDA receptors. The most well-known medication is ketamine, which acts as an NMDA antagonist. Other types of NMDA receptor antagonists have been developed, such as esketamine (S-ketamine), which is the enantiomer of ketamine. They have a rapid and pronounced antidepressant effect but are temporary. They serve as a good alternative for treatment-resistant depression, but toxicity and addiction issues may arise.