PDE inhibitors in psychiatry--future options for dementia, depression and schizophrenia?
Phosphodiesterases are key enzymes in cellular signalling pathways. They degrade cyclic nucleotides and their inhibition via specific inhibitors offers unique 'receptor-independent' opportunities to modify cellular function. An increasing number of in vitro and animal model studies point to innovative treatment options in neurology and psychiatry. This review critiques a selection of recent studies and developments with a focus on dementia/neuroprotection, depression and schizophrenia. Despite increased interest among the clinical neurosciences, there are still no approved PDE inhibitors for clinical use in neurology or psychiatry. Adverse effects are a major impediment for clinical approval. It is therefore necessary to search for more specific inhibitors at the level of different PDE sub-families and isoforms.
Halene
Tobias B
TB
SMRI Laboratory for Experimental Therapeutics in Psychiatry, Department of Psychiatry, University of Pennsylvania, Translational Research Laboratories, 125 S. 31st Street, Philadelphia, PA 19104, United States.
Siegel
Steven J
SJ
D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use; D003704:Dementia / Q000188:drug therapy*; D003863:Depression / Q000188:drug therapy*; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D018696:Neuroprotective Agents; D010726:Phosphodiesterase Inhibitors