PDE10A inhibitors: an assessment of the current CNS drug discovery landscape

Curr Opin Drug Discov Devel. 2009 Jul;12(4):458-67.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antipsychotic Agents / chemistry
  • Antipsychotic Agents / pharmacology*
  • Antipsychotic Agents / therapeutic use
  • Basal Ganglia / drug effects
  • Basal Ganglia / enzymology
  • Drug Discovery*
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Neurons / drug effects
  • Neurons / enzymology
  • Phosphodiesterase Inhibitors / chemistry
  • Phosphodiesterase Inhibitors / pharmacology*
  • Phosphodiesterase Inhibitors / therapeutic use
  • Phosphoric Diester Hydrolases / metabolism*
  • Protein Binding
  • Schizophrenia / drug therapy

Substances

  • Antipsychotic Agents
  • Ligands
  • Phosphodiesterase Inhibitors
  • PDE10A protein, human
  • Phosphoric Diester Hydrolases