Novel antipsychotic agents: recent advances in the drug treatment of schizophrenia

Several new potential antipsychotic agents have been disclosed in the patent literature over the last 3 years and a sizeable number of drugs are actually in advanced stages of investigation. The majority of these cases involve compounds characterised by a high affinity for dopamine or 5-HT2A receptors, associated or not to low dopamine receptor affinity or by affinity for other serotonin receptors such as 5-HT6 and 5-HT7, which may indirectly modulate mesolimbic dopaminergic neurons, producing efficacy against positive and negative symptoms of schizophrenia. Other patents have focused on chemical entities capable of relieving schizophrenic symptoms by interaction with less obvious receptors, such as glutamate or sigma receptors. A few patents claim the development of atypical antipsychotic drugs, structurally related to olanzapine and aripiprazole, characterised by high efficacy and low propensity to induce motor disturbances and blood disorders. Starting from the typical antipsychotics, taking into account the challenging pharmacological profile of clozapine, olanzapine and aripiprazole, this update will focus on the recent and ongoing activity in the development of novel antipsychotic drugs.