Hopwood S E, Owesson C A, Callado L F, McLaughlin D P, Stamford J A
Academic Department of Anaesthesia and Intensive Care, St Bartholomew's and The Royal London School of Medicine and Dentistry, Royal London Hospital, Whitechapel, UK.
J Psychopharmacol. 2001 Sep;15(3):147-53. doi: 10.1177/026988110101500301.
The atypical analgesic tramadol has strong structural similarities to the antidepressant venlafaxine and is a mixed noradrenaline (NA) and serotonin (5-HT) uptake inhibitor. Because tramadol has been found active in the forced swim test, a common predictor of antidepressant efficacy, we therefore examined the effects of chronic tramadol on various pre- and post-synaptic monoamine measures. Male Wistar rats (150-200 g) received tramadol (20 mg/kg i.p.) or vehicle for 21 days and were sacrificed 24 h after the last dose. Quantitative autoradiography revealed that specific frontocortical [3H]dihydroalprenolol and [3H]ketanserin binding was lower in the chronic tramadol group than controls (beta: 37+/-8 and 217+/-56 fmol/mg; 5-HT2A: 23+/-3 and 44+/-7 fmol/mg, respectively, p < 0.05). Chronic tramadol had no effect on the magnitude of electrically stimulated noradrenaline (NA) efflux or uptake in locus coeruleus (LC) slices. Although dexmedetomidine (10 nM) decreased LC NA efflux equally (by approximately 60%) in chronic tramadol and vehicle groups, desipramine (50 nM) increased LC NA efflux more in vehicle (to 164+/-7%) than tramadol-treated rats (144+/-6%; p < 0.05). Chronic tramadol had no effect on dorsal raphé (DRN) or median raphé (MRN) 5-HT efflux. However, 5-HT uptake in tramadol-treated rats was slower (p < 0.05) in MRN and nearly so (p = 0.055) in DRN. The selective 5-HT1A agonist 8-OH-DPAT reduced 5-HT efflux in both DRN and MRN. Its effect in DRN was greater in rats given chronic tramadol than in vehicle controls (54+/-2 versus 32+/-6% reduction in 5-HT efflux, respectively). In conclusion, we suggest that tramadol has many of the pre- and postsynaptic neurochemical features of a conventional antidepressant, as might be predicted from its pharmacology.
非典型镇痛药曲马多与抗抑郁药文拉法辛在结构上有很强的相似性，是一种去甲肾上腺素（NA）和5-羟色胺（5-HT）的混合摄取抑制剂。由于曲马多在强迫游泳试验中已被发现有活性，而强迫游泳试验是抗抑郁疗效的一种常见预测指标，因此我们研究了慢性给予曲马多对各种突触前和突触后单胺指标的影响。雄性Wistar大鼠（150 - 200克）接受曲马多（20毫克/千克腹腔注射）或赋形剂，持续21天，并在最后一剂后24小时处死。定量放射自显影显示，慢性曲马多组前额皮质特异性的[3H]二氢阿普洛尔和[3H]酮舍林结合低于对照组（β：分别为37±8和217±56飞摩尔/毫克；5-HT2A：分别为23±3和44±7飞摩尔/毫克，p < 0.05）。慢性给予曲马多对蓝斑（LC）切片中电刺激诱发的去甲肾上腺素（NA）外流或摄取量没有影响。虽然右美托咪定（10纳摩尔）在慢性曲马多组和赋形剂组中同样降低了LC的NA外流（约60%），但地昔帕明（50纳摩尔）使赋形剂组的LC NA外流增加得更多（达到164±7%），而曲马多处理组的大鼠增加到144±6%（p < 0.05）。慢性给予曲马多对中缝背核（DRN）或中缝正中核（MRN）的5-HT外流没有影响。然而，曲马多处理组大鼠中MRN的5-HT摄取较慢（p < 0.05），DRN中也接近这种情况（p = 0.055）。选择性5-HT1A激动剂8-OH-DPAT降低了DRN和MRN中的5-HT外流。在慢性给予曲马多的大鼠中，它对DRN的作用比对赋形剂对照组更大（5-HT外流分别降低54±2%和32±6%）。总之，我们认为曲马多具有许多传统抗抑郁药的突触前和突触后神经化学特征，这从其药理学上或许可以预测到。
