Phosphodiesterase Type 4 Inhibition in CNS Diseases
| Autor: | Arjan Blokland, Pim R. A. Heckman, Rudy Schreiber, Dean Paes, Jos Prickaerts, Tim Vanmierlo |
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| Rok vydání: | 2019 |
| Předmět: |
STRUCTURAL BASIS
0301 basic medicine Central nervous system Brain damage Toxicology Bioinformatics DOUBLE-BLIND 03 medical and health sciences 0302 clinical medicine THERAPEUTIC STRATEGY Central Nervous System Diseases BINDING medicine Animals Humans BRAIN Adverse effect Acquired brain injury Neuroinflammation Pharmacology business.industry Mechanism (biology) Multiple sclerosis MEMORY Phosphodiesterase medicine.disease Cyclic Nucleotide Phosphodiesterases Type 4 030104 developmental biology medicine.anatomical_structure HIPPOCAMPUS Phosphodiesterase 4 Inhibitors CAMP PDE4 medicine.symptom business SUBCELLULAR-LOCALIZATION 030217 neurology & neurosurgery |
| Zdroj: | Trends in Pharmacological Sciences. 40:971-985 |
| ISSN: | 0165-6147 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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