PHENCYCLIDINES (KETAMINE)

History

Phencyclidine was the first drug of its class to be used for anesthesia. It was synthesized by Maddox and introduced into clinical use in 1958 by Greifenstein and colleagues^[440] and in 1959 by Johnstone and associates.^[441] Although phenyclidine proved useful as an anesthetic, it produced unacceptably high adverse psychological effects (hallucinations and delirium) in the postanesthetic recovery period. Cyclohexamine, a congener of phencyclidine, was tried clinically in 1959 by Lear and coworkers,^[442] but it was found to be less efficacious than phencyclidine in terms of analgesia and yet had as many adverse psychotomimetic effects. Neither of these drugs is used clinically today, although phencyclidine is available for illicit recreational use. Ketamine (Ketalar) was synthesized in 1962 by Stevens and was first used in humans in 1965 by Corssen and Domino.^[443] It was chosen from among 200 phencyclidine derivatives and proved to be the most promising in laboratory animal testing. Ketamine was released for clinical use in 1970 and is still used in a variety of clinical settings. Ketamine is different from most other anesthetic induction agents in that it has significant analgesic effect. It does not usually depress the cardiovascular and respiratory systems,^{[285] [444]} but it does possess some of the worrisome adverse psychological effects found with the other phencyclidines. Ketamine consists of two stereoisomers: S-(+) and R-(-). The S-(+)-isomer is more potent and is associated with fewer side effects. Interest in ketamine has recently increased because of its effects on hyperalgesia and opiate tolerance, as well as the availability (in some countries) of S-(+)-ketamine.