Probing targets for antipsychotic drug action with PET and SPET receptor imaging

The use of in vivo receptor imaging by positron emission tomography (PET) a nd single photon emission tomography (SPET) has permitted exploration of ta rgets 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 d rugs. The dopamine hypothesis of antipsychotic drug action suggests that cl inical response is directly related to the level of striatal D2/D3 receptor occupancy of antipsychotic drugs. This may be true for classical antipsych otic drugs, but recent evidence suggests that novel, atypical antipsychotic drugs produce efficacy in association with modest and transient striatal D 2/D3 receptor occupancy levels. Furthermore, atypical antipsychotic drugs a ppear to show preferential occupancy of limbic cortical dopamine D2 recepto rs. Cortical dopamine D2/D2-like receptors may be a common site of action f or all antipsychotic drugs. Data from receptor challenge paradigms has high lighted the need to explore the neurotransmitter systems involved in regula ting or stabilising dopamine transmission, tither via dopamine autoreceptor s or non-dopaminergic pathways. These may be promising targets for drug dev elopment. In vivo PET and SPET imaging has produced unique data contributin g to the design of better, less toxic drugs for schizophrenia. ((C) 2001 Li ppincott Williams & Wilkins).