A potential novel antidepressant target based on phosphodiesterase 4: Research advances / 国际药学研究杂志

ABSTRACT

Depression is a prevalent and life-threatening mental disorder. Its mechanisms remain unclear. It was found that depressive disorders are closely related to monoamine neurotransmitters absence, down-regulation of hypothalamic-pituitary-adrenal (HPA) axis and neurotrophic factors and dendritic complexity in brain. Phosphodiesterase 4 (PDE4) inhibitor rolipram produce antidepressant and memory-enhancing effects via intracellular cAMP signaling. However, its clinical utility is limited by the major side effect of emesis, which appears to be PDE isoform-specific. Therefore, this research is to investigate whether long-form PDED variants mediate antidepressant and cognition-enhancing effects, without causing emesis. This review summaries the PDE molecular structure, distribution and its antidepressant function, so as to illustrate the advantage of selective subtype inhibitor in the treatment of depression.