Role of imidazoline receptors in modulation of muscle tone and pain

咪唑啉受体在调节肌张力和疼痛中的作用

• 批准号: 12672124
• 负责人: ONO Hideki
• 金额: $ 2.11万
• 依托单位: Graduate School, Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672124/
• 关键词: 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

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.

自 20 世纪 80 年代以来，研究表明可乐定（所谓的 α_2-肾上腺素受体激动剂）与咪唑啉受体结合并通过中枢神经系统产生低血压。在本研究中，我们旨在阐明咪唑啉受体在介导咪唑啉的肌肉松弛和镇痛作用中的作用。 1．大鼠脊髓反射研究和行为研究表明，替扎尼定的肌肉松弛作用是由于对咪唑啉受体的影响而不是对α_2-肾上腺素受体的影响。 (2000-2001)2．替扎尼定不会使 ddY 品系小鼠产生肌肉松弛作用。由此筛选出替扎尼定产生肌肉松弛作用的小鼠品系。我们在旋转棒试验中发现C57BL/6小鼠对替扎尼定敏感。建议咪唑啉受体参与这种肌肉松弛。 （2001）3。研究了咪唑啉受体在可乐定镇痛作用中的作用。虽然可乐定对机械引起的疼痛的镇痛作用被α_2-肾上腺素受体拮抗剂育亨宾完全阻断，但对热引起的疼痛的镇痛作用却被育亨宾部分拮抗。残留成分被咪唑啉受体拮抗剂消除。这些结果表明可乐定对热引起的疼痛的镇痛作用部分是由咪唑啉受体介导的。 (2002)咪唑啉受体有I1、I2和I3亚型。进一步研究这些亚型与上述功能之间的关系以及选择性药物的开发有助于治疗多种类型的中枢神经系统病变患者的痉挛和疼痛。

项目成果

Honda, M., Sekiguchi, Y., Sato, N., Ono, H.: "Involvement of imidazoline receptors in the centrally acting muscle-relaxant effects of tizanidine"Eur. J. Pharmacol.. 445. 187-193 (2002)

Honda, M.、Sekiguchi, Y.、Sato, N.、Ono, H.：“咪唑啉受体参与替扎尼定的中枢肌肉松弛作用”Eur。

Motoko Honda et al.: "Involvement of imidazoline receptors in the centrally acting muscle-relaxant effects of tizanidine"European Journal of Pharmacology. 445. 187-193 (2002)

Motoko Honda 等人：“咪唑啉受体参与替扎尼定的中枢肌肉松弛作用”欧洲药理学杂志。

Sekiguchi, Y., Honda, M., Ono, H.: "Effects of tizanidine, a centrally acting muscle relaxant, on spinal reflex potentials in rats, with special reference to imidazoline receptors"Frontiers of Mechanisms of Memory and Dementia, Kato, T.ed., Excerpta Medic

Sekiguchi, Y.、Honda, M.、Ono, H.：“替扎尼定（一种中枢作用的肌肉松弛剂）对大鼠脊髓反射电位的影响，特别是咪唑啉受体”记忆和痴呆机制前沿，Kato，

Sekiguchi,Y.,Honda,M. and Ono,H.: "Effects of tizanidine, a centrally acting muscle relaxant, on spinal reflex potentials in rats, with special reference to imidazoline receptors"Frontiers of the Mechanisms of Memory and Dementia, Kato T.ed., Excerpta Med

关口，Y.，本田，M.

Honda, M,. Sekiguchi, Y., Sato, N. & Ono, H.: "Involvement of imidazoline receptors in the centrally acting muscle-relaxant effects of tizanidine"Eur. J. Parmacol.. 445. 187-193 (2002)

本田，M，.