Ketamine: History, Contemporary Perspective, and New Opportunities. A Narrative Review

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Abstract
Ketamine, an N-methyl-D-aspartate receptor antagonist, developed more than 60 years ago as an anesthetic, has experienced a varied history but remains relevant in modern global medical practice. Over the past several decades, it has revealed new potential extending far beyond anesthesia. There is growing interest in the use of subdissociative doses of ketamine to treat various types of acute and chronic pain and depression. Its efficacy is similar to that of opioids, with a low incidence of transient adverse effects. Ketamine can be administered via multiple routes and is nearing the status of an ideal analgesic for the prehospital setting because of its favorable safety profile. In patients with severe trauma, ketamine is likely the optimal analgesic, as it provides hemodynamic stability without an increase in intracranial pressure. Ketamine is particularly useful in patients with opioid dependence, opioid tolerance, or opioid-induced hyperalgesia. The discovery of its multiple molecular targets and related effects enables the use of this unique agent in many areas of clinical and experimental medicine, including anesthesiology, emergency medicine, intensive care, pain management, psychiatry, research on the neurobiological basis of consciousness, and modeling of pathological mental states. This article presents the history of ketamine development and reviews current understanding of its mechanisms of action, methods, and areas of application.

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