Role of imidazoline receptors in modulation of muscle tone and pain

自20世纪80年代以来，研究表明可乐定(α_2-肾上腺素能受体激动剂)与咪唑啉受体结合，通过中枢神经系统产生降压作用。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。大鼠脊髓反射和行为学研究表明，替扎尼定的肌肉松弛作用是通过影响咪唑啉受体而不是α_2-肾上腺素能受体实现的。(2000-2001)2.替扎尼定不能在ddy品系小鼠身上产生肌肉松弛。从而筛选出替扎尼定产生肌肉松弛的小鼠品系。在旋转棒试验中，我们发现C57BL/6小鼠对替扎尼定敏感。提示咪唑啉受体参与了这种肌肉松弛。(2001)3.研究了咪唑啉受体参与可乐定的镇痛作用。可乐定对机械性疼痛的镇痛作用可被α_2受体拮抗剂育亨宾完全阻断，但对热致痛的镇痛作用可被育亨宾部分拮抗。残留成分可被咪唑啉受体拮抗剂消除。以上结果提示，可乐定对热痛的镇痛作用部分是通过咪唑啉受体介导的。(2002)咪唑啉受体分为I1、I2和I3三种亚型。进一步研究这些亚型与上述功能的关系以及选择性药物的开发，对于治疗多种类型的中枢神经系统损害患者的痉挛和疼痛具有重要意义。

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.