Ketamine and phencyclidine: the good, the bad and the unexpected

The history of ketamine and phencyclidine from their development as potential clinical anaesthetics through drugs of abuse and animal models of schizophrenia to potential rapidly acting antidepressants is reviewed. The discovery in 1983 of the NMDA receptor antagonist property of ketamine and phency...

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Bibliographic Details
Published in:British journal of pharmacology 2015-09, Vol.172 (17), p.4254-4276
Main Authors: Lodge, D, Mercier, M S
Format: Article
Language:English
Subjects:
Animals
Antidepressive Agents - metabolism
Antidepressive Agents - pharmacology
Antidepressive Agents - therapeutic use
Excitatory Amino Acid Antagonists - metabolism
Excitatory Amino Acid Antagonists - pharmacology
Excitatory Amino Acid Antagonists - therapeutic use
Humans
Ketamine - metabolism
Ketamine - pharmacology
Ketamine - therapeutic use
Phencyclidine - metabolism
Phencyclidine - pharmacology
Phencyclidine - therapeutic use
Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors
Receptors, N-Methyl-D-Aspartate - metabolism
Reviews
Schizophrenia
Schizophrenia - drug therapy
Schizophrenia - metabolism
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Summary:The history of ketamine and phencyclidine from their development as potential clinical anaesthetics through drugs of abuse and animal models of schizophrenia to potential rapidly acting antidepressants is reviewed. The discovery in 1983 of the NMDA receptor antagonist property of ketamine and phencyclidine was a key step to understanding their pharmacology, including their psychotomimetic effects in man. This review describes the historical context and the course of that discovery and its expansion into other hallucinatory drugs. The relevance of these findings to modern hypotheses of schizophrenia and the implications for drug discovery are reviewed. The findings of the rapidly acting antidepressant effects of ketamine in man are discussed in relation to other glutamatergic mechanisms.
ISSN:0007-1188
1476-5381
DOI:10.1111/bph.13222