Novel targets for drugs in schizophrenia.
Since the discovery of the first antipsychotic drug, chlorpromazine, in the early 1950s, all effective antipsychotic drugs have been found to share the common property of dopamine D2 receptor antagonism. There has been some suggestion that simple D2 receptor antagonism may not confer optimal antipsychotic efficacy. Currently available antipsychotic drugs leave many symptoms of the illness untreated and cause unacceptable side effects. Recent research in schizophrenia suggests a number of potential new non-D2 targets for pharmacotherapy including glutamate, acetylcholine and serotonin neurotransmitter systems. This review summarises the main neurochemical theories of schizophrenia, and, in the light of these, examines possible therapeutic targets for new antipsychotic drugs.
Stone
J M
JM
Section of Neurochemical Imaging, Kings College London Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK. j.stone@iop.kcl.ac.uk
Pilowsky
L S
LS
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D018377:Neurotransmitter Agents / Q000502:physiology; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism
D014150:Antipsychotic Agents; D018377:Neurotransmitter Agents; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D018698:Glutamic Acid