Cel
To identify the receptors in brain which are targets for the antipsychotic effect of neuroleptic drugs. This information will be a cornerstone in future industrial antipsychotic drug development.
To develop principles for more effective, safe and tolerable clinical antipsychotic drug treatment of the more than l million currently treated patients in Europe.
More than l million patients within the EU suffer from schizophrenia and are on long-term treatment with antipsychotic drugs. The direct health care costs for schizophrenia are higher than 10 billion ECU's per year. Insufficient treatment response and intolerable side effects lead to relapse in psychosis and a chronic course. The industrial development of more effective drugs is hampered by the high costs. At least 150 million ECU's are required to develop a new antipsychotic. To improve clinical treatment and to speed up drug development it is of central importance to identify the targets for antipsychotic drug effects in the human brain. Research now benefits from the development of new imaging techniques such as Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT). The sensitivity of these techniques is unsurpassed for direct studies on drug binding in the living human brain. High binding to receptors for the neurotransmitter dopamine has been demonstrated by PET in large brain nuclei which are related to motor side effects. We have now developed the first method in the world that allows quantitative examination of dopamine receptor binding in the small limbic and cortical brain regions which are assumed to be "sites" for the antipsychotic effect. To obtain the required number of patients three PET-centres will use the same strategy to examine patients treated with antipsychotic drugs. Relationships will be examined among dose, drug concentration in plasma and degree of drug binding in brain. Principles will thereby be identified for optimal clinical treatment of schizophrenia. Biochemical targets for antipsychotic drug effects will be identified in distinct regions of the human brain . The new data can be used in industrial programs to tailor more selective, efficacious and tolerable drugs for the treatment of schizophrenia SPECT is a widespread technique with potential for routine clinical optimisation of treatment. To validate the SPECT-methodology a direct clinical comparison will be made between PET and SPECT.
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171 76 STOCKHOLM
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