Research Advances in Phosphodiesterase Inhibitors for the Treatment of Depression

doi:10.19803/j.1672-8629.20250626

Abstract

Abstract: Objective To review the mechanisms of action, advances in research, and clinical potential of phosphodiesterase inhibitors (PDEIs) for the treatment of depression. Methods Such databases as PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI) were searched for related literature. The retrieved studies were screened and analyzed to summarize the classification of PDEs, their neuroregulatory mechanisms, and preclinical and clinical findings related to depression. Results PDEIs were found to produce antidepressant effects in various animal models primarily by modulating cyclic adenosine monophosphate (cAMP)/cyclic guanosine monophosphate (cGMP) signaling pathways. These effects involved enhancement in neuronal plasticity, regulation of neurotransmitter release, and attenuation of neuroinflammatory responses. Inhibitors targeting specific subtypes, such as phosphodiesterase-4 (PDE4) and phosphodiesterase-5 (PDE5), showed such potential advantages as rapid onset of action and cognitive improvement in preclinical and some clinical studies. However, challenges persisted, including gastrointestinal side effects and variable blood-brain barrier penetration efficiency. Conclusion PDEIs are promising as an emerging class of therapeutic agents for depression. Subsequent research should focus on optimizing subtype selectivity, developing advanced drug delivery systems, and exploring rational combination therapies to maximize their clinical utility.

Key words: Phosphodiesterase Inhibitors, Depression, Neuroinflammation, Antidepressant Drugs, Mechanism of Action, Therapeutic Advances

CLC Number:

R971

LIU Meng, FANG Ke, ZHANG Yuan, ZHANG Zhen, WEI Liangbing. Research Advances in Phosphodiesterase Inhibitors for the Treatment of Depression[J]. Chinese Journal of Pharmacovigilance, 2025, 22(10): 1188-1193.

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https://zgywjj.magtechjournal.com/EN/Y2025/V22/I10/1188

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