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

Br J Pharmacol. 2015 Sep;172(17):4254-76. doi: 10.1111/bph.13222. Epub 2015 Jul 28.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 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
  • Schizophrenia / drug therapy
  • Schizophrenia / metabolism

Substances

  • Antidepressive Agents
  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Ketamine
  • Phencyclidine