| Autor: |
Saeko Takase, Jingzhu Liao, Yue Liu, Rinako Tanaka, Yasuhiro Miyagawa, Masahito Sawahata, Akira Sobue, Hiroyuki Mizoguchi, Taku Nagai, Kozo Kaibuchi, Norio Ozaki, Kiyofumi Yamada |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
European journal of pharmacology. 931 |
| ISSN: |
1879-0712 |
| Popis: |
Current antipsychotics used to treat schizophrenia have associated problems, including serious side effects and treatment resistance. We recently identified a significant association of schizophrenia with exonic copy number variations in the Rho GTPase activating protein 10 (ARHGAP10) gene using genome-wide analysis. ARHGAP10 encodes a RhoGAP superfamily member that is involved in small GTPase signaling. In mice, Arhgap10 gene variations result in RhoA/Rho-kinase pathway activation. We evaluated the pharmacokinetics of fasudil and hydroxyfasudil using liquid chromatography-tandem mass spectrometry in mice. The antipsychotic effects of fasudil on hyperlocomotion, social interaction deficits, prepulse inhibition deficits, and novel object recognition deficits were also investigated in a MK-801-treated pharmacological mouse schizophrenia model. Fasudil and its major metabolite, hydroxyfasudil, were detected in the brain at concentrations above their respective K |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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