期刊
CURRENT PHARMACEUTICAL DESIGN
卷 17, 期 2, 页码 137-150出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/138161211795049624
关键词
Basal ganglia; Phosphodiesterase 10A; PDE10A; schizophrenia; psychosis; antipsychotic; cAMP/PKG; cGMP/PKG; signalling cascades; dopamine; pro-cognitive; striatopallidal; striatonigral; PDE10A structure
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 D-1 receptor signalling, and concomitant inhibition of dopamine D-2 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.
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