Kim D, Murray M, Simansky K J
Department of Neurobiology and Anatomy, MCP Hahnemann University, Philadelphia, PA 19102, USA.
Exp Neurol. 2001 Jun;169(2):496-500. doi: 10.1006/exnr.2001.7660.
The direct serotonergic agonist, m-chlorophenylpiperazine (m-CPP), displays high efficacy at 5-HT(2C) receptors. Systemic administration of m-CPP increased dramatically the percentage of weight-supported steps made on a treadmill by rats with complete midthoracic spinal transections. The improvement in motor function occurred in rats with grafts of fetal spinal cord into the site of transection (transplant rats) and in spinal rats without grafts (spinal rats). m-CPP produced a therapeutic action with its first administration and after 14 single daily injections. In contrast, the serotonin and norepinephrine reuptake inhibitor, chlorimipramine (CMI), failed to enhance weight support during 21 days of treatment. The results imply that stimulating directly 5-HT(2C) receptors restores postural support after spinal injury. Thus, 5-HT(2C) agonists are candidates for treating spinal patients chronically without the development of tolerance.
直接血清素能激动剂间氯苯哌嗪（m-CPP）对5-HT(2C)受体具有高效能。对完全性胸段脊髓横断的大鼠进行全身给药后，m-CPP显著增加了其在跑步机上支撑体重的步数百分比。运动功能的改善出现在将胎儿脊髓移植到横断部位的大鼠（移植大鼠）以及未进行移植的脊髓大鼠中。m-CPP在首次给药时以及每日单次注射14次后均产生了治疗作用。相比之下，血清素和去甲肾上腺素再摄取抑制剂氯米帕明（CMI）在21天的治疗期间未能增强体重支撑能力。这些结果表明，直接刺激5-HT(2C)受体可恢复脊髓损伤后的姿势支撑。因此，5-HT(2C)激动剂是长期治疗脊髓损伤患者且不会产生耐受性的候选药物。
