The central nervous system is endowed with complex mechanisms of defense. However, these protection mechanisms fail in
the presence of risk factors such as genetic mutations, environmental factors (bisphenol A, polycyclic aromatic hydrocarbons (PAHs),
polyfluoroalkyl chemicals) or social stress and psychiatric disorders (anxiety, depression, psychosis, attention deficits) appear. Critical
psychiatric conditions treatment consists in administration of antidepressants and antipsychotics drugs. These drugs are widely prescribed,
but their efficiency in controlling mental symptoms is an important point in current clinical studies.
Antidepressants and antipsychotics register several side effects and their interactions with other polycyclic aromatic hydrocarbons are
well established. Research is focused upon reducing these side effects and understanding their pharmacodynamic and pharmacokinetic
properties in order to develop advanced methods to predict induced pharmacological events. Here we intend to detail recent advances in
the field of structure-activity relationship (QSAR) applied to antidepressants and antipsychotics with polycyclic aromatic structure as last
generation drugs used in central nervous system disorders. We present the biological activity of large series of psychiatric drugs predicted
by 2D and 3D-QSAR dependent and independent molecules alignment. Predicted biological activities were correlated with common
pharmaceutical descriptors as steric, electronic hydrogen donor/acceptor bond but also new components of QSAR models as membrane
ions’ contributions to the antagonism of these drugs at membrane receptors are presented. The paper refers both to preclinical tested
molecules and to already known antidepressants and antipsychotics based on a large variety of polycyclic aromatic structure. Drug potency
decrease in the presence of PAHs is also discussed.