| Project/Area Number |
12672124
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Graduate School, Nagoya City University |
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Principal Investigator |
ONO Hideki Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究科, 教授 (00080200)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | imidazoline receptors / clonidine / tizanidine / spinal reflet / muscle relaxation / Analgesic Action / 筋弛緩作用 / 抗痙縮作用 / 単シナプス反射 |
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| Research Abstract |
Since 1980s it has been shown that clonidine (so-called α_2-adrenoceptor agonist) binds to imidazoline receptors and produce hypotention via central nervous systems. In the present study, we aimed to elucidate the role of imidazoline receptors in the mediation of muscle relaxation and analgesic action of imidazolines.
1. Spinal reflex study and behavioural study in rats showed that the muscle relaxant effects of tizanidine was due to the effects on imidazoline receptors but not α_2-adrenoceptors. (2000-2001)
2. Tizanidine does not produce muscle relaxation in ddY strain mice. Thus the mouse strain in which tizanidine produce muscle relaxation was screened. We found that C57BL/6 mice were sensitive to tizanidine in rota-rod test. Involvement of imidazoline receptors in this muscle relaxation was suggested. (2001)
3. Involvement of imidazoline receptors in analgesic action of clonidine was studied. Although analgesic action of clonidine on mechanically-induced pain was completely blocked by α_2-adrenoceptor antagonist yohimbine, the analgesic action on heat-induced pain was partially antagonized by yohimbine. The residual component was abolished by imidazoline receptor antagonist. These results suggested that the analgesic actions of clonidine on heat-induced pain were partially mediated by imidazoline receptors. (2002)
There are I1, I2 and I3 subtypes in imidazoline receptors. Further studies on relation between these subtypes and above mentioned functions and development of selective drug are useful in treating spasticity and pain in many types of CNS lesioned patients.
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