Extrastriatal and striatal D2 dopamine receptor blockade with haloperidol or new antipsychotic drugs in patients with schizophrenia

Background Both traditional and atypical antipsychotics have been hypothesised to be effective in schizophrenia through limbic and cortical D2 dopamine receptor blockade. Aims To investigate this hypothesis with the D2/D3-selective positron emission tomography (PET) probe [76Br]-FLB457. Method PET scans were performed on 6 controls and 18 patients with schizophrenia treated with haloperidol or with risperidone, clozapine, amisulpride or olanzapine. Results The D2 dopamine receptor blockade was high in the temporal cortex with both haloperidol and atypical antipsychotics. The atypicals, however, induced a significantly lower D2 binding index than haloperidol in the thalamus and in the striatum. Conclusions Results suggest that cortical D2 dopamine receptors are a common target of traditional and atypical antipsychotics for therapeutic action. Higher in vivo binding to the D2 receptors in the cortex than in the basal ganglia is suggested as an indicator of favourable profile for a putative antipsychotic compound.