Future therapies for schizophrenia

Abstract

Despite decades of research, the aetiology of schizophrenia remains elusive. However, the recent success of atypical antipsychotic drugs such as clozapine and risperidone has broken a 30 year trend during which pharmaceutical companies focused solely on D2 receptor antagonism in their quest for new drug treatments for schizophrenia. In the next few years, at least four other new atypical antipsychotics, olanzapine, sertindole, seroquel and ziprasidone, will be introduced throughout the developed world. It is likely that atypical compounds such as these will largely displace the typical neuroleptics, which provide only limited efficacy and produce unpleasant side-effects. The majority of the patents taken out in recent years remain focussed on the traditional notions of dopamine blockade, but there is an increasing trend in industry to select D1, D3 and D4 receptors as targets for potential drugs, rather than the D2 subtype. Greater emphasis is now being placed on the serotonergic hypothesis of schizophrenia, as more ligands selective for serotonin receptors are developed. A large number of companies have combined both theories in an effort to produce improved versions of clozapine; thus the serotonin-dopamine antagonist (SDA) class of compounds has emerged. Such drugs certainly display fewer extrapyramidal side-effects than traditional neuroleptics and there is considerable hope that they may prove more effective in the treatment of negative symptoms. Patent applications for radically different compounds have also appeared during 1995 and 1996, including some based on the glutamatergic and developmental theories of schizophrenia. These potential new therapies are reviewed.