Evolution of schizophrenia drugs: a focus on dopaminergic systems

Many of the drugs currently marketed for the treatment of schizophrenia are dopamine D2 receptor antagonists or partial agonists with or without mixed receptor pharmacology, and primarily treat the positive symptoms of schizophrenia. These drugs, depending on their pharmacological profile, have been categorized as typical (with low or no serotonergic component) and atypical (with a high serotonergic, 5-HT2A and 5-HT1A component) antipsychotics. Atypical antipsychotics have increased tolerability compared with typical antipsychotics, particularly against extrapyramidal side effects which are caused by D2 receptor antagonism, and an increased efficacy for the treatment of the negative symptoms associated with schizophrenia. However, over the course of treatment, adverse effects such as weight gain, metabolic disorders, QT prolongation and sexual dysfunction have been observed, and thus current research efforts are being directed to the identification of new antipsychotics that have better tolerability and efficacy against the positive and negative symptoms of schizophrenia.