title: Ketamine and phencyclidine: the good, the bad and the unexpected.
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.
authors.affiliation: Centre for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, Bristol, UK.
authors.forename: D
authors.initials: D
authors.lastname: Lodge
authors.affiliation: Centre for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, Bristol, UK.
authors.forename: M S
authors.initials: MS
authors.lastname: Mercier
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007649:Ketamine / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D010622:Phencyclidine / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D010622:Phencyclidine