Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan.
Department of Pharmacology, Nippon Medical School, Tokyo, Japan.
Int J Neuropsychopharmacol. 2014 Jun;17(6):845-50. doi: 10.1017/S1461145713001764. Epub 2014 Jan 15.
Tramadol is used for the treatment of pain, and it is generally believed to activate the μ-opioid receptor and inhibit serotonin (5-HT) and norepinephrine (NE) transporters. Recent findings from animal experiments suggest that 5-HT reuptake inhibition in brain is related to pain reduction. However, there has been no report of 5-HT transporter (5-HTT) occupancy by tramadol at clinical doses in humans. In the present study, we investigated 5-HTT occupancy by tramadol in five subjects receiving various doses of tramadol by using positron emission tomography (PET) scanning with the radioligand [11C]DASB. Our data showed that mean 5-HTT occupancies in the thalamus by single doses of tramadol were 34.7% at 50 mg and 50.2% at 100 mg. The estimated median effective dose (ED50) of tramadol was 98.1 mg, and the plasma concentration was 0.33 μg/ml 2 h after its administration; 5-HTT occupancy by tramadol was dose-dependent. We estimated 5-HTT occupancy at 78.7% upon taking an upper limit dose (400 mg) of tramadol. The results of the present study support the finding that 5-HTT inhibition is involved in the mechanism underlying the analgesic effect of tramadol in humans, and a clinical dose of tramadol sufficiently inhibits 5-HTT reuptake; this inhibition is similar to that shown by selective serotonin reuptake inhibitors (SSRIs).
曲马多用于治疗疼痛，一般认为其通过激活μ-阿片受体和抑制 5-羟色胺（5-HT）和去甲肾上腺素（NE）转运体发挥作用。动物实验的最新发现表明，大脑中 5-HT 再摄取的抑制与疼痛减轻有关。然而，在人类中，尚未有曲马多在临床剂量下对 5-HT 转运体（5-HTT）的占有率的报告。在本研究中，我们使用放射性配体 [11C]DASB 通过正电子发射断层扫描（PET）扫描，研究了 5 名接受不同剂量曲马多的受试者中曲马多对 5-HTT 的占有率。我们的数据显示，单剂量曲马多在丘脑的平均 5-HTT 占有率在 50mg 时为 34.7%，在 100mg 时为 50.2%。曲马多的估计中位有效剂量（ED50）为 98.1mg，给药后 2 小时血浆浓度为 0.33μg/ml；曲马多的 5-HTT 占有率呈剂量依赖性。我们估计曲马多最高剂量（400mg）时的 5-HTT 占有率为 78.7%。本研究的结果支持以下发现，即 5-HTT 抑制参与了曲马多在人类中的镇痛作用机制，临床剂量的曲马多足以抑制 5-HTT 再摄取；这种抑制类似于选择性 5-羟色胺再摄取抑制剂（SSRIs）。
