Development of anti-Parkinson's disease drugs using P-glycoprotein knockout mice heated with endogenous neurotoxin.
| Project/Area Number |
18390037
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Drug development chemistry
|
|---|
| Research Institution | Hiroshima University |
|---|
Principal Investigator |
OHTA Shigeru Hiroshima University, Graduate School of Biomedical Sciences, Professor (60160503)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KOTAKE Yaichiro Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor (20335649)
SUGIHARA Kazumi Hiroshima University, Graduate School of Biomedical Sciences, Assistant Professor (20271067)
|
|---|
| Project Period (FY) |
2006 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥15,760,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2007: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2006: ¥9,000,000 (Direct Cost: ¥9,000,000)
|
|---|
| Keywords | parkinsonism / tetrahydroisoquinoline / P-glycoprotein / neurotxin / prodrug |
|---|
| Research Abstract |
The purpose of this research is to find anti-Parkinson's disease agent from 1-methyl-tetrahydroisoquinoline derivatives. Hydroxy derivatives have high effect, but they are difficult to penetrate of blood-brain barrier, because of their water solubility.
The ester group was introduced to the hydroxylated 1-methyl tetrahydroisoquinoline derivatives. They had better anti-parkinsonism effect than hydroxyl derivatives. The second purpose of this study is the examination of the relationship between parkinsonism and the transport characteristics (influx/outflux) of tetrahydroisoquinolines across the blood-brain barrier. At first, to examine the substrate specificity of tetrahydroisoquinolines as P-glycoprotein (P-gp) substrates.
These results indicate that 3',4'DHBnTIQ, an endogenous parkinsonism-inducing neurotoxin, is a P-gp substrate.
These results may also suggest that P-gp inactivation and/or dysfunction in the brain are closely related to the induction of Parkinson's disease.
|
Report
(3 results)
Research Products
(26 results)
-
-
-
-
-
-
-
-
-
[Journal Article] Ohta, "Glutamate excitotoxicity is involved in cell death caused by tributyltin in cultured rat cortical neurons."2006
Author(s)
Yusuke, Nakatsu, Yaichiro, Kotake, Kazuya, Komasaka, Hiroko, Hakozaki, Ryota, Taguchi, Toshiaki, Kume, Akinori, Akaike, Shigeru
-
Journal Title
Toxicol. Sci 89
Pages: 235-242
Description
「研究成果報告書概要(欧文)」より
Related Report
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] A Parkinson's disease-related neurotoxin binds to tubulin.2007
Author(s)
Ryuki, Kohta, Yaichiro, Kotake, Shunsuke, Izumi, Kazumi, Sugihara, Takamitsu, Hosoya, Toshiyuki, Hiramatsu, Yuko, Ohtsubo, Hiroko, Koyama, Masaaki, Suzuki, Shigeru, Ohta
Organizer
Neuro 2007
Place of Presentation
Yokohama
Year and Date
2007-09-12
Description
「研究成果報告書概要(欧文)」より
Related Report
-
-
-
-
-
