Abstract

Disturbances of the basal ganglia processes is heavily involved in schizophrenia. Phosphodiesterase 10A (PDE10A) is a basal ganglia specific hydrolase, which plays an essential role in regulating cAMP/PKA and cGMP/PKG signalling cascades by controlling the magnitude, duration and cellular location of cAMP/cGMP elevation. Biochemical and behavioral data indicate that PDE10A inhibition activates cAMP/PKA signalling in the basal ganglia, leading to the potentiation of dopamine D1 receptor signalling, and concomitant inhibition of dopamine D2 receptor signalling. Preclinical evidence in a range of animal models suggests that a PDE10A inhibitor could provide efficacy on positive, cognitive and negative symptoms of schizophrenia and PDE10A inhibitors are currently being evaluated in clinical trials for the treatment of schizophrenia.

Keywords: Basal ganglia, Phosphodiesterase 10A, PDE10A, schizophrenia, psychosis, antipsychotic, cAMP/PKG, cGMP/PKG, signalling cascades, dopamine, pro-cognitive, striatopallidal, striatonigral, PDE10A structure