Ketamine was synthesized in 1962 by Parke Davis and first used in humans in 1965 [1,2]. The United States military used ketamine as a field anesthetic during the Vietnam War, and the agent gradually gained popularity for use in brief surgical procedures as both an induction and maintenance agent for general anesthesia.
By the 1970s, ketamine became a widely used recreational drug, with street names such as K, Special K, Kitkat, Vitamine K, Ket, and Super K. Ketamine abuse is closely associated worldwide with the use of other "club drugs" including "ecstasy" (3,4-methylenedioxymethamphetamine or MDMA), gamma hydroxybutyrate (GHB), and methamphetamine, often in the setting of large dance parties (sometimes referred to as raves) .
Ketamine is produced by a complicated, multistep synthesis that essentially precludes clandestine drug production. Most if not all ketamine sold illicitly in the United States is obtained by diversion of legitimate supplies.
This topic review will discuss the presentation and treatment of ketamine intoxication, as well as poisoning with ketamine analogues, including methoxketamine, methoxetamine, tiletamine, xylazine, and similar substances. A summary table to facilitate emergent management is provided (table 1). Discussions of the use of ketamine for procedural sedation and induction for rapid sequence intubation (RSI) are found elsewhere. (See "Procedural sedation in adults", section on 'Ketamine' and "Sedation or induction agents for rapid sequence intubation in adults", section on 'Ketamine' and "Pharmacologic agents for pediatric procedural sedation outside of the operating room", section on 'Ketamine'.)
Ketamine is an arylcycloalkylamine that is structurally related to phencyclidine (PCP). Ketamine is a dissociative anesthetic and hallucinogen. It acts primarily as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, but also possesses some opioid receptor activity and sympathomimetic properties. The latter results in enhanced central and peripheral monoaminergic transmission and inhibition of central and peripheral cholinergic transmission . The primary site of ketamine's CNS activity appears to be the thalamocortical projection system, where it causes depression of certain cortical and thalamic functions and stimulation of parts of the limbic system .