Phosphodiesterase 10 inhibitors: new disease modifying drugs for Parkinson's disease?

Phosphodiesterases (PDEs), as key regulators of cyclic nucleotides, and their inhibitors have been emerged as new pharmacological targets and promising drug candidates for many diseases, including central nervous system pathologies. The high level of PDE10A expression in the striatal medium spiny neurons suggests a prominent function role for the isoenzyme. Basal ganglia dysfunction is associated with neuropsychiatric disorders and until recently the development of PDE10A inhibitors has been focused on schizophrenia. Currently, the pharmaceutical research on PDE10A inhibitors is moving to show the modulation of other functions associated with the basal ganglia such the motor control. Thus, PDE10A inhibitors may be important pharmacological agents for neurodegenerative disorders such as Parkinson's and Huntington's diseases. Recent data supporting new clues for PDE10A as therapeutic target together with a concise review of the chemical structures of its inhibitors are provided here. The goal of this manuscript is to provide new ideas for assistant pharmacologist and medicinal chemists in the search for PDE10A inhibitors as new disease modifying drugs for Parkinson's disease.