Title:Phosphodiesterase as a Target for Cognition Enhancement in Schizophrenia
Volume: 20
Issue: 26
Author(s): Mayasah Y. Al-Nema and Anand Gaurav*
Affiliation:
- Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur,Malaysia
Keywords:
Schizophrenia, Dopamine system dysfunction, Glutamatergic neurotransmission, Antipsychotic drugs, Cognitive
impairment, Phosphodiesterases.
Abstract: Schizophrenia is a severe mental disorder that affects more than 1% of the population worldwide.
Dopamine system dysfunction and alterations in glutamatergic neurotransmission are strongly implicated
in the aetiology of schizophrenia. To date, antipsychotic drugs are the only available treatment
for the symptoms of schizophrenia. These medications, which act as D2-receptor antagonist, adequately
address the positive symptoms of the disease, but they fail to improve the negative symptoms and cognitive
impairment. In schizophrenia, cognitive impairment is a core feature of the disorder. Therefore, the
treatment of cognitive impairment and the other symptoms related to schizophrenia remains a significant
unmet medical need. Currently, phosphodiesterases (PDEs) are considered the best drug target for the
treatment of schizophrenia since many PDE subfamilies are abundant in the brain regions that are relevant
to cognition. Thus, this review aims to illustrate the mechanism of PDEs in treating the symptoms
of schizophrenia and summarises the encouraging results of PDE inhibitors as anti-schizophrenic drugs
in preclinical and clinical studies.