A Review of the Mechanism of Antagonism of N-methyl-D-aspartate Receptor by Ketamine in Treatment-resistant Depression

• Published in: Curēus (Palo Alto, CA) Vol. 10; no. 5; p. e2652
• Main Authors: Sattar, Yasar, Wilson, John, Khan, Ali M, Adnan, Mahwish, Azzopardi Larios, Daniel, Shrestha, Shristi, Rahman, Quazi, Mansuri, Zeeshan, Hassan, Ali, Patel, Nirav B, Tariq, Nargis, Latchana, Sharaad, Lopez Pantoja, Stefany C, Vargas, Sadiasept, Shaikh, Naveed A, Syed, Fawaduzzaman, Mittal, Daaman, Rumesa, Fatima
• Format: Journal Article
• Language: English
• Published: United States Cureus Inc 18.05.2018; Cureus
• Subjects: Anesthesiology; Antidepressants; Brain-derived neurotrophic factor; Ketamine; Kinases; Mental depression; Neurology; Psychiatry; Rodents; Suicides & suicide attempts; New York; United States > US; Texas; depression; nmda antagonist; ketamine; nmda receptor; suicide
• ISSN: 2168-8184; 2168-8184
• DOI: 10.7759/cureus.2652

The biochemical processes involved in depression go beyond serotonin, norepinephrine, and dopamine. The N-methyl-D-aspartate (NMDA) receptor has a major role in the neurophysiology of depression. Ketamine, one of the prototypical NMDA antagonists, works rapidly in controlling depressive symptoms, including acutely suicidal behavior, by just a single injection. Ketamine may rapidly increase the glutamate levels and lead to structural neuronal changes. Increased neuronal dendritic growth may contribute to synaptogenesis and an increase in brain-derived neurotrophic factor (BDNF). Activation of the mechanistic target of rapamycin (mTOR), as well as increased levels of BDNF, may increase long-term potentiation and result in an improvement in the symptoms of depression. The mechanisms of ketamine's proposed effect as an off-label treatment for resistant depression are outlined in this paper.