TAK ‐063, a novel PDE 10A inhibitor with balanced activation of direct and indirect pathways, provides a unique opportunity for the treatment of schizophrenia
Article Swipe
Kazunori Suzuki
,
Haruhide Kimura
·
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1111/cns.12798
YOU?
·
· 2018
· Open Access
·
· DOI: https://doi.org/10.1111/cns.12798
Summary The basal ganglia regulates motor, cognitive, and emotional behaviors. Dysfunction of dopamine system in this area is implicated in the pathophysiology of schizophrenia characterized by positive symptoms, negative symptoms, and cognitive deficits. Medium spiny neurons ( MSN s) are principal output neurons of striatum in the basal ganglia. Similar to current antipsychotics with dopamine D 2 receptor antagonism or partial agonism, phosphodiesterase 10A ( PDE 10A) inhibitors activate indirect pathway MSN s, leading to the expectation of therapeutic potential for the treatment of psychosis. PDE 10A inhibitors also activate direct pathway MSN s which may be associated with cognitive functions. These pathways have competing effects on antipsychotic‐like activities and extrapyramidal symptoms in rodents. Therefore, careful consideration of activation pattern of these pathways by a PDE 10A inhibitor is critical to produce potent efficacy and superior safety profiles. In this review, we outline the pharmacological profile of TAK ‐063, a novel PDE 10A selective inhibitor. Our study revealed that off‐rates of PDE 10A inhibitors may characterize their pharmacological profiles via regulation of each MSN pathway. TAK ‐063, with a faster off‐rate property, could provide a unique opportunity as a novel therapeutic approach to treatment of psychosis and cognitive deficits in schizophrenia. TAK ‐063 also has a therapeutic potential in other basal ganglia disorders.
Related Topics
Concepts
Neuroscience
Basal ganglia
Schizophrenia (object-oriented programming)
Dopamine
Medium spiny neuron
Psychosis
Antipsychotic
Striatum
Indirect pathway of movement
Neurochemical
Psychology
Pharmacology
Medicine
Central nervous system
Psychiatry
Metadata
- Type
- review
- Language
- en
- Landing Page
- https://doi.org/10.1111/cns.12798
- https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cns.12798
- OA Status
- hybrid
- Cited By
- 28
- References
- 74
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2782698452
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2782698452Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1111/cns.12798Digital Object Identifier
- Title
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TAK ‐063, a novelPDE 10A inhibitor with balanced activation of direct and indirect pathways, provides a unique opportunity for the treatment of schizophreniaWork title - Type
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reviewOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2018Year of publication
- Publication date
-
2018-01-09Full publication date if available
- Authors
-
Kazunori Suzuki, Haruhide KimuraList of authors in order
- Landing page
-
https://doi.org/10.1111/cns.12798Publisher landing page
- PDF URL
-
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cns.12798Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/cns.12798Direct OA link when available
- Concepts
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Neuroscience, Basal ganglia, Schizophrenia (object-oriented programming), Dopamine, Medium spiny neuron, Psychosis, Antipsychotic, Striatum, Indirect pathway of movement, Neurochemical, Psychology, Pharmacology, Medicine, Central nervous system, PsychiatryTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
28Total citation count in OpenAlex
- Citations by year (recent)
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2025: 3, 2024: 4, 2022: 3, 2021: 9, 2020: 2Per-year citation counts (last 5 years)
- References (count)
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74Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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