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Atypical antipsychotics may be defined as drugs that produce antipsychotic action with minimal extrapyramidal symptoms, although their effects on negative symptoms and in refractory patients are also of interest. All the currently available atypical antipsychotics (clozapine, risperidone, olanzapine, and sertindole) share only 1 pharmacological property that distinguishes them from typical antipsychotics in humans: they block a high number of serotonin₂ receptors (>80%) and a low to modest number of D₂ receptors (eg, 20%-70% for clozapine and 60%-80% for risperidone and olanzapine).^1-2 This contrasts with the typical antipsychotics that block mainly the dopamine D₂ receptors and have minimal, if any, serotonin₂ receptor occupancy.

If high serotonin₂ occupancy and low to modest D₂ occupancy is the key to atypical antipsychotic properties,^2-3 it should be feasible to obtain the appropriate serotonin₂/D₂ effects by using a combination of 2 drugs: 1 that is a serotonin₂ antagonist and another that is a D₂ antagonist. . . . [Full Text of this Article]

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