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Review
. 2024 Nov:229:116516.
doi: 10.1016/j.bcp.2024.116516. Epub 2024 Aug 30.

Ketamine - An Imperfect Wonder Drug?

Tanner Magruder  1 , Marielle Isenhart  1 , Maximillian V Striepe  1 , Andrew Mannisto  1 , Karry M Jannie  1 , Jolene Smith  1 , Kenneth E McCarson  2 , Daniel T Christian  1 , Vanja Duric  3
Affiliations
Review

Ketamine - An Imperfect Wonder Drug?

Tanner Magruder et al. Biochem Pharmacol. 2024 Nov.

Abstract

Ketamine is a potent sedative and dissociative anesthetic agent that has been used clinically for over 50 years since it was first developed in the 1960 s as an alternative to phencyclidine (PCP). When compared to PCP, ketamine exhibited a much lower incidence of severe side effects, including hallucinations, leading to its increased popularity in clinical practice. Ketamine was initially used as an anesthetic agent, especially in emergency medicine and in surgical procedures where rapid induction and recovery was necessary. However, over the last few decades, ketamine was found to have additional clinically useful properties making it effective in the treatment of a variety of other conditions. Presently, ketamine has a wide range of clinical uses beyond anesthesia including management of acute and chronic pain, as well as treatment of psychiatric disorders such as major depression. In addition to various clinical uses, ketamine is also recognized as a common drug of abuse sought for its hallucinogenic and sedative effects. This review focuses on exploring the different clinical and non-clinical uses of ketamine and its overall impact on patient care.

Keywords: Abuse; Analgesia; Anesthesia; Antidepressant; Hallucinogen; Ketamine.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1.
Figure 1.
Ketamine’s pharmacological versatility underlies its progression into a standard medication used throughout different clinical settings including prehospital, intraoperative, and post-operative areas.
Figure 2.
Figure 2.
Proposed dose-dependent mechanisms of action for the anesthetic, psychotomimetic /hallucinogenic, analgesic and antidepressant effects of ketamine.
Figure 3:
Figure 3:
Cellular and molecular mechanisms underlying rapid-antidepressant effects of ketamine likely involve inhibition of NMDA receptors located on GABAergic inhibitory interneurons in the prefrontal cortex (PFC). Downstream disinhibition of presynaptic glutamatergic neurons leads to BDNF-dependent activation of postsynaptic mTOR signaling and subsequent increase in synaptic function.
See this image and copyright information in PMC

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