Atypical antipsychotics; serotonin receptors; serotonin and dopamine antagonists; schizophrenia; efficacy; tolerability

TThe introduction of atypical, i.e. second generation, antipsychotics (AAPs) since the discovery of clozapine, has been a big step in schizophrenia treatment. They are ‘atypical’ as their clinical profile differs from typical (first-generation) antipsychotics. All AAPs share dopamine and serotonin receptor antagonism (except for amisulpride, which preferentially binds to dopamine D2/D3 receptors). Besides antagonism to the dopamine D2 receptor, the AAPs also block other dopamine receptors such as D1, D3, or D4 [1]. The serotonergic system modulates a broad spectrum of the central nervous system functions through 5-HT binding to 5-HT receptors. The overwhelming majority of research has focused on 5-HT2A receptors antagonism. However, a variety of 5-HT receptors, such as 5-HT2A/2C, 5-HT1A, 5-HT3, 5-HT6, and 5-HT7 receptors, may contribute to the mechanisms of action of ‘atypicality’ [2]. For example, we have data indicating that 5-HT3 receptor antagonists (ondansentron) as adjunctive therapy can improve negative symptoms in schizophrenia [3]. Other molecular targets are also relevant for further AAPs characterization. Some AAPs act at adrenergic alpha 1/2, histamine (especially H1) and muscarinic receptors. Targeting glutamatergic neurotransmission may be also involved. Clinical characteristics of individual AAPs can be predicted according to their molecular profile