| Project/Area Number |
17390042
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Osaka University |
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Principal Investigator |
AZUMA J Osaka University, Graduate School of Pharmaceutical Sciences, Professor, 薬学研究科, 教授 (30144463)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIO Y Osaka University, Graduate School of Pharmaceutical Sciences, associate professor, 薬学研究科, 助教授 (20359839)
KINOSHITA T Kansai Medical University, Medical School, Professor, 医学部, 教授 (20186290)
KATO M Kansai Medical University, Medical School, research associate, 医学部, 助手 (00351510)
FUKUDA T Osaka University, Graduate School of Pharmaceutical Sciences, research associate, 薬学研究科, 助手 (10423120)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2006: ¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 2005: ¥8,500,000 (Direct Cost: ¥8,500,000)
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| Keywords | drug responsiveness / SSRI / SNRI / CYP2D6 / Fluvoxamine / serotonin transporter / serotonin receptor / セロトニントランスポーター |
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| Research Abstract |
This research was focused on inter-individual difference in the efficacy of Selective Serotonin Reuptake Inhibitor (SSRI) and Selective Serotonin Norepinephrine Reuptake Inhibitor (SNRI). The aim of the study was to promote the individualized medicine in this field by using responsible genetic information that could predict individual response to SSRI/SNRIs.
In the line of comparative clinical trials between fluvoxamine and paroxetine and between paroxetine and milnaciplan, which had been going on from 2003 and was newly set up, respectively, we tried to identify the possible genetic factors including pharmacokinetics and pharmacodynamic factors.
First, we confirmed that plasma fluvoxamine concentrations were affected by CYP2D6 polymorphism and smoking status. Next, we found that the linked polymorphic region of the serotonin transporter gene contributed to the efficacy of SSRIs and serotonin receptor 2A polymorphism was associated with adverse drug reaction. In addition, we selected the single nucleotide polymorphisms in the tryptophan hydroxylase 2 and dopamine receptor 2 as a possible candidate to modify the response to SSRIs, and showed that these SNPs could be a modulator. On the other hand, genetic factors mentioned above were not associated with response to milnaciplam, but possibly done the polymorphism in an adrenalin receptor gene.
Our findings identified the characteristics of each SSRI/SNRIs with genetic factors, and provided the possibility to promise individualized medicine by the appropriate choice of drugs according to the genetic background of individuals and characteristics of drugs, although prospective clinical trial is necessary to use this kind of information.
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