QSAR Approaches Applied to Antidepressants Induced Neurogenesis - in vivo and in silico Applications

Brain presents very complex advanced protective mechanisms. However, these mechanisms occasionally fail due to risk factors represented by genetic, environmental or social stress and consequently, severe psychiatric disorders such as depression, schizophrenia or psychotic depression are induced. Under such circumstances, latest strategies in experimental and in silico neuroscience consider essential to identify new applications of already clinically-approved drugs for the treatment of psychiatric disorders but also as promoters of neurogenesis and neurites outgrowth. Results of recent studies suggested that antidepressants are able to induce neurogenesis and neurites outgrowth by their agonistic effects on 5-hydroxytryptamine receptor (5-HT), especially 5-HT1A, and sigma1 receptor (σ1R), but many molecular aspects of these processes are still unclear. Here we present structural aspects of molecular complexes (5-HT1A and σ1R and their ligands) revealed by experimental and in silico studies. Here we present the chemical structures-biological activity relationship (SAR) of these molecules revealed by recent experimental and in silico studies, offering a new perspective on the antidepressants mechanism as neurogenesis and neurites outgrowth promoters.