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
Current Pharmaceutical Design
Title: PDE10A Inhibitors: Novel Therapeutic Drugs for Schizophrenia
Volume: 17 Issue: 2
Author(s): Jan Kehler and Jacob Nielsen
Affiliation:
Keywords: Basal ganglia, Phosphodiesterase 10A, PDE10A, schizophrenia, psychosis, antipsychotic, cAMP/PKG, cGMP/PKG, signalling cascades, dopamine, pro-cognitive, striatopallidal, striatonigral, PDE10A structure
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.
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Cite this article as:
Kehler Jan and Nielsen Jacob, PDE10A Inhibitors: Novel Therapeutic Drugs for Schizophrenia, Current Pharmaceutical Design 2011; 17 (2) . https://dx.doi.org/10.2174/138161211795049624
DOI https://dx.doi.org/10.2174/138161211795049624 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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