PDE10A inhibitors: an assessment of the current CNS drug discovery landscape.
PDE10A is a dual substrate PDE that is highly expressed in medium spiny neurons of the striatal complex. The inhibition of PDE10A produces effects that modulate basal ganglia function in ways that suggest a particular therapeutic utility in the treatment of psychosis in schizophrenia. Significant understanding of PDE10A at the molecular level has helped to guide efforts in inhibitor design, and many different inhibitor classes have now been discovered. At least one PDE10A inhibitor has been advanced into clinical trials to begin to test the hypothesis that such agents may be useful in the treatment of psychosis.
Chappie
Tom
T
Pfizer Inc, Neuroscience Medicinal Chemistry, Groton, CT 06340, USA. thomas.a.chappie@pfizer.com
Humphrey
John
J
Menniti
Frank
F
Schmidt
Chris
C
D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001479:Basal Ganglia / Q000187:drug effects / Q000201:enzymology; D055808:Drug Discovery; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011485:Protein Binding; D012559:Schizophrenia / Q000188:drug therapy
D014150:Antipsychotic Agents; D008024:Ligands; D010726:Phosphodiesterase Inhibitors; C119843:PDE10A protein, human; D010727:Phosphoric Diester Hydrolases