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.
Keywords: 5-hydroxytryptamine receptors, antidepressants, neurites, neurogenesis, QSAR, sigma-1 receptor.
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