Genetics of novel therapeutic targets in schizophrenia

Abstract

For many years, following the introduction of chlorpromazine in the 1950s, little progress was made in the discovery of new drugs for schizophrenia (Reynolds, 1992). Dopamine D2 receptor blockade was recognised as the only therapeutic target for antipsychotics (Creese et al, 1976) and the inevitable consequences of striatal blockade remained problematic. However, the strategies and stimuli for discovery of new drugs changed with the introduction of new, atypical antipsychotics in the 1990s. These include clozapine, remoxipride (now withdrawn), olanzapine, risperidone and sertindole (Kerwin & Taylor, 1996). The goal of antipsychotic drug development has always been to widen the therapeutic ratio between efficacy and adverse effects. These new drugs have in the main achieved this. However, which therapeutic targets these drugs employ remains a mystery, and this information is clearly important for future research into more selectively targeted agents.