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PDE10A Inhibitors: Novel Therapeutic Drugs for Schizophrenia

[ Vol. 17 , Issue. 2 ]


Jan Kehler and Jacob Nielsen   Pages 137 - 150 ( 14 )


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.


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


, Ottiliavej 9, DK-2500 valby,Denmark/ H. Lundbeck A/S dept. Medicinal chemistry.

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