Clin Psychopharmacol Neurosci.  2025 Feb;23(1):15-31. 10.9758/cpn.24.1229.

In the Brain of Phosphodiesterases: Potential Therapeutic Targets for Schizophrenia

• Barbagallo F
• Assenza MR
• Messina A

• KMID: 2565657
• DOI: http://doi.org/10.9758/cpn.24.1229

Abstract

Intracellular cyclic nucleotides (cyclic adenosine monophosphate and cyclic guanosine monophosphate) and downstream cellular signal transduction are regulated by phosphodiesterases (PDEs). The neuroplasticity, neurotransmitter pathways, and neuroinflammation-controlling functions of PDEs were demonstrated in numerous in vitro and animal model studies. We comprehensively reviewed the literature regarding the expression of PDEs in various brain regions. Subsequently, articles regarding schizophrenia and PDEs were examined. The pathophysiological mechanisms of schizophrenia and PDEs in preclinical and clinical investigations are briefly reviewed. Particularly for those who do not respond to conventional antipsychotics, specific PDE inhibitors may offer innovative therapeutic alternatives. Although the connection between schizophrenia and PDEs is intriguing, additional research is required. Comprehending the brain’s PDE isoforms, their therapeutic potential, and any adverse effects of inhibiting them is essential for progress in this field.

Keyword

Neuroinflammatory diseases; Phosphodiesterase inhibitors; Adenosine cyclic monophosphate; Guanosine cyclic monophosphate; Neuronal plasticity; Schizophrenia