Hunskaar S, Rosland J H, Hole K
Department of Physiology, University of Bergen, Norway.
Eur J Pharmacol. 1989 Jan 24;160(1):83-91. doi: 10.1016/0014-2999(89)90656-0.
The possible involvement of central serotonergic pathways in the mechanism of action of orphenadrine citrate was investigated in male albino mice. Orphenadrine (20 mg/kg) did not alter the concentration of 5-hydroxytryptamine (5-HT) or its metabolite 5-hydroxyindole acetic acid in the frontal cortex or spinal cord, nor did it, in moderate concentrations, inhibit the uptake of [14C]5-HT, [3H]noradrenaline ([3H]NA) or [3H]dopamine ([3H]DA) into crude synaptosomal preparations from the cortex. The antinociceptive effect of orphenadrine was studied in the formalin test and in the increasing temperature hot plate test. No sensorimotor impairment was observed for doses of 30 mg/kg or lower. A general depletion of serotonin by means of p-chlorophenylalanine significantly reduced the effect of orphenadrine in both tests, while lesion of the ascending serotonergic systems by means of p-chloroamphetamine did not affect the analgesia. It is concluded that the antinociceptive effect of orphenadrine may be mediated in part via the raphe-spinal serotonergic systems.
在雄性白化小鼠中研究了中枢5-羟色胺能通路在枸橼酸奥芬那君作用机制中的可能参与情况。奥芬那君（20mg/kg）并未改变额叶皮质或脊髓中5-羟色胺（5-HT）及其代谢产物5-羟吲哚乙酸的浓度，中等浓度时也未抑制[14C]5-HT、[3H]去甲肾上腺素（[3H]NA）或[3H]多巴胺（[3H]DA）摄取到来自皮质的粗制突触体标本中。在福尔马林试验和升温热板试验中研究了奥芬那君的抗伤害感受作用。30mg/kg及以下剂量未观察到感觉运动损害。通过对氯苯丙氨酸使5-羟色胺普遍耗竭，在两项试验中均显著降低了奥芬那君的作用，而通过对氯苯丙胺损伤上行5-羟色胺能系统并不影响镇痛作用。得出结论，奥芬那君的抗伤害感受作用可能部分通过中缝脊髓5-羟色胺能系统介导。
