Ketamine: An Update on Cellular and
Subcellular Mechanisms with Implications for
Clinical Practice
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abstract
Background: Ketamine is one of the oldest hypnotic agents used to provide an anesthetic agent
with analgesic properties and minimal suppressive effects on respiration. The ability of ketamine
in modulating glutamatergic (N-methyl D-aspartate) pain receptors has made this anesthetic drug
a new option for the management of patients with chronic pain syndromes. Further preclinical
and clinical findings suggest ketamine may have wide ranging effects on both cognition and
development. Recent advances have revealed an unprecedented role for ketamine in the acute
management of depression.
Objectives: The purpose of this review is to integrate a number of basic science, preclinical,
and clinical studies with the goal of providing insight into the possible signaling events underlying
ketamine’s biological effects in pain management, depression, cognition and memory, and
neurodevelopment.
Study Design: Narrative literature review.
Setting: Health science library.
Methods: A comprehensive literature search was performed for the following medical subject
headings and keywords (ketamine, anesthesia, pain, analgesia, depression, NMDA receptors) on
PubMed, Google Scholar, and Medline from 1966 to the present time. The search was then limited
to those in the English language. The full text of the relevant articles were printed and reviewed
by all authors.
Results: We provided a comprehensive review of the literature that explored the pharmacologic
aspects of ketamine from its conception as an anesthetic to its evolution as a drug used for
treatment of depression and pain. To address the patient response variability observed in clinical
studies, we have provided possible patient-specific factors that could contribute to outcome
variability.
Limitations: Like any review, this study was limited by publication bias and missing information
on negative studies which were denied publication.
Conclusions: Ketamine, an old anesthetic agent with analgesic properties, is currently being
considered for treating patients with chronic pain and depression. The complex pharmacological
characteristics of ketamine make this medication a multifaceted therapeutic option in these cases.
Key Words: Ketamine, anesthetics, pain, depression, pharmacology
