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http://hdl.handle.net/1942/30430
Title: | Phosphodiesterase Type 4 Inhibition in CNS Diseases | Authors: | Blokland, A Heckman, P VANMIERLO, Tim Schreiber, R PAES, Dean Prickaerts, J |
Issue Date: | 2019 | Publisher: | ELSEVIER SCIENCE LONDON | Source: | TRENDS IN PHARMACOLOGICAL SCIENCES, 40 (12) , p. 971 -985 | Abstract: | Phosphodiesterases (PDEs) have been an interesting drug target for many diseases. Although a vast number of mainly preclinical studies demonstrates beneficial effects of PDE inhibitors for central nervous system (CNS) diseases, no drugs are currently available for CNS indications. In this review, we discuss the rationale of PDE4 inhibitors for different CNS diseases, including memory impairments, striatal disorders, multiple sclerosis (MS), and acquired brain injury (ABU). However, clinical development has been problematic due to mechanism-based adverse effects of these drugs in humans. Our increased understanding of factors influencing the conformational state of the PDE4 enzyme and of how to influence the binding affinity of PDE4 subtype inhibitors, holds promise for the successful development of novel selective PDE4 inhibitors with higher efficacy and fewer adverse effects. | Document URI: | http://hdl.handle.net/1942/30430 | ISSN: | 0165-6147 | e-ISSN: | 1873-3735 | DOI: | 10.1016/j.tips.2019.10.006 | ISI #: | WOS:000499077400006 | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2020 |
Appears in Collections: | Research publications |
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File | Description | Size | Format | |
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1-s2.0-S0165614719302329-main.pdf Restricted Access | Published version | 2.26 MB | Adobe PDF | View/Open Request a copy |
Manuscript.pdf | Peer-reviewed author version | 280.04 kB | Adobe PDF | View/Open |
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