| Project/Area Number |
21590597
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Applied pharmacology
|
|---|
| Research Institution | Oita University |
|---|
Principal Investigator |
OHASHI Kyoichi 大分大学, 医学部・臨床薬理学, 教授 (20137714)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
UCHIDA Shinya 静岡県立大学, 薬学部・実践薬学分野, 講師 (80372522)
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
SHIRAO Kuniaki 大分大学, 医学部・腫瘍内科学, 教授 (10467996)
NOGUCHI Takayuki 大分大学, 医学部・麻酔科学, 医学部長、教授 (90156183)
KOTEGAWA Tsutomu 大分大学, 医学部・臨床薬理学, 准教授 (20264343)
MORIMOTO Takuya 大分大学, 医学部附属病院・臨床薬理センター, 准教授 (10392242)
IMAI Hiromitsu 大分大学, 医学部・臨床薬理学, 助教 (30398250)
TATEISHI Masato 長崎国際大学, 薬学部・臨床薬剤学, 教授 (20446123)
|
|---|
| Project Period (FY) |
2009 – 2011
|
| Project Status |
Completed (Fiscal Year 2011)
|
| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2011: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2010: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2009: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
|
|---|
| Keywords | ゲノム / 薬剤反応性 / オピオイド / オピオイド鎮痛薬 / μ受容体 / 遺伝子多型 / 個別化治療 / オピオイド受容体 |
|---|
| Research Abstract |
Opioid analgesics exert their therapeutic effects by binding to theμ-opioid receptor(MOR). More than 100 variants in theμ-receptor gene(OPRM1) have been identified, which include at least 20 polymorphic mutants that cause amino acid substitutions, thereby affecting the response of theμ-receptor. The clinical usefulness of A118G in exon-1 of the OPRM1 gene which result in an amino acid substitution from asparagine to aspartate at position 40(Asn40Asp) was studied. The allele frequency of 118G is 41% in our Japanese healthy-volunteers, on the other hand, 10-20% of Caucasian is reported. In order to examine the functional significance of the A118G gene mutation, clinical studies have been conducted in both healthy subjects and cancer patients. We have founded that cancer pain patients with 118GG who were treated with oxycodone or fentanyl were observed less frequency of adverse reactions including nausea, vomiting and sleepiness than that with 118AA, although no clear difference was observed on the pain threshold. Moreover, we have studied the effects of buprenorphine,μreceptor partial agonist, in healthy volunteers with 118GG or 118AA. Although pharmacokinetics of buprenorphine of the two groups were similar, 118GG group were significantly lower sensitiveness of pain threshold and VAS ratings of sleepiness, fatigue, nausea and euphoria. The genetic polymorphism of OPRM1 c. 118 position may affect the sensitivity ofμopioid receptor and may become a useful biomarker in the opioid pain therapy.
|
