Probing targets for antipsychotic drug action with PET and SPET receptor imaging.
The use of in vivo receptor imaging by positron emission tomography (PET) and single photon emission tomography (SPET) has permitted exploration of targets for antipsychotic drug action in living patients. Early PET and SPET studies focused on striatal D2 dopamine receptors. There is broad agreement that unwanted extrapyramidal (parkinsonian) side effects of antipsychotic drugs result from high striatal dopamine D2/D3 receptor blockade by these drugs. The dopamine hypothesis of antipsychotic drug action suggests that clinical response is directly related to the level of striatal D2/D3 receptor occupancy of antipsychotic drugs. This may be true for classical antipsychotic drugs, but recent evidence suggests that novel, atypical antipsychotic drugs produce efficacy in association with modest and transient striatal D2/D3 receptor occupancy levels. Furthermore, atypical antipsychotic drugs appear to show preferential occupancy of limbic cortical dopamine D2 receptors. Cortical dopamine D2/D2-like receptors may be a common site of action for all antipsychotic drugs. Data from receptor challenge paradigms has highlighted the need to explore the neurotransmitter systems involved in regulating or stabilising dopamine transmission, either via dopamine autoreceptors or non-dopaminergic pathways. These may be promising targets for drug development. In vivo PET and SPET imaging has produced unique data contributing to the design of better, less toxic drugs for schizophrenia.
Pilowsky
L S
LS
Institute of Nuclear Medicine, UCL, Middlesex Hospital, London. l.Pilowsky@iop.kcl.ac.uk
D014150:Antipsychotic Agents / Q000494:pharmacology*; D006801:Humans; D009420:Nervous System / Q000000981:diagnostic imaging; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D014055:Tomography, Emission-Computed; D015899:Tomography, Emission-Computed, Single-Photon
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2