Honda Motoko, Sekiguchi Yuko, Sato Naoko, Ono Hideki
Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Japan.
Eur J Pharmacol. 2002 Jun 12;445(3):187-93. doi: 10.1016/s0014-2999(02)01664-3.
The centrally acting muscle relaxant tizanidine has an imidazoline structure and binds not only to alpha(2)-adrenoceptors but also to imidazoline receptors. The role of imidazoline receptors in the muscle-relaxant effect of tizanidine was studied using the alpha(2)-adrenoceptor/imidazoline receptor antagonist idazoxan and the alpha(2)-adrenoceptor antagonist yohimbine. Tizanidine decreased the spinal mono- and polysynaptic reflexes in intact rats, and the inhibitory effects were antagonized by idazoxan but not by yohimbine. After pretreatment with prazosin, tizanidine decreased the mono- and polysynaptic reflexes in spinalized rats. While yohimbine partly inhibited tizanidine-induced depression of the polysynaptic reflex, idazoxan completely abolished tizanidine-induced depression of spinal reflexes. Furthermore, tizanidine-induced muscle relaxation in the traction test was significantly inhibited by idazoxan but not by yohimbine. From these results, it is suggested that imidazoline receptors, but not alpha(2)-adrenoceptors, are involved in the supraspinal inhibitory effects of tizanidine on spinal reflexes, and at the spinal level, alpha(2)-adrenoceptors and imidazoline receptors are involved in the inhibitory effects of tizanidine.
中枢性肌松药替扎尼定具有咪唑啉结构，不仅能与α₂ - 肾上腺素能受体结合，还能与咪唑啉受体结合。使用α₂ - 肾上腺素能受体/咪唑啉受体拮抗剂伊达唑啉和α₂ - 肾上腺素能受体拮抗剂育亨宾，研究了咪唑啉受体在替扎尼定肌松作用中的作用。替扎尼定可降低完整大鼠的脊髓单突触和多突触反射，且这种抑制作用可被伊达唑啉拮抗，但不能被育亨宾拮抗。用哌唑嗪预处理后，替扎尼定可降低脊髓大鼠的单突触和多突触反射。虽然育亨宾可部分抑制替扎尼定诱导的多突触反射抑制，但伊达唑啉可完全消除替扎尼定诱导的脊髓反射抑制。此外，在牵引试验中，伊达唑啉可显著抑制替扎尼定诱导的肌肉松弛，而育亨宾则无此作用。从这些结果表明，咪唑啉受体而非α₂ - 肾上腺素能受体参与了替扎尼定对脊髓反射的脊髓上抑制作用，并且在脊髓水平，α₂ - 肾上腺素能受体和咪唑啉受体均参与了替扎尼定的抑制作用。
