Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet and Stockholm County Council, Stockholm, Sweden.
Int J Neuropsychopharmacol. 2019 Jan 1;22(1):53-56. doi: 10.1093/ijnp/pyy089.
Tramadol, a centrally acting analgesic drug, has relatively high affinity to serotonin transporter and norepinephrine transporter in addition to μ-opioid receptor. Based on this characteristic, tramadol is expected to have an antidepressant effect.
Positron emission tomography measurements with [11C]MADAM and [18F]FMeNER-D2 were performed at baseline and after i.v. administration of 3 different doses (1, 2, and 4 mg/kg) of tramadol using 6 cynomolgus monkeys. The relationship between dose and occupancy for serotonin transporter and norepinephrine transporter was estimated.
Tramadol occupied similarly both serotonin transporter (40%-72%) and norepinephrine transporter (7%-73%) in a dose-dependent manner. The Kd was 2.2 mg/kg and 2.0 mg/kg for serotonin transporter and norepinephrine transporter, respectively.
Both serotonin transporter and norepinephrine transporter of in vivo brain were blocked at >70% at a clinically relevant high dose of tramadol. This study suggests tramadol has potential antidepressant effects through the inhibition of serotonin transporter and norepinephrine transporter in the brain.
曲马多是一种中枢作用的镇痛药，除了μ-阿片受体之外，它对 5-羟色胺转运体和去甲肾上腺素转运体也具有较高的亲和力。基于这一特性，曲马多有望具有抗抑郁作用。
使用 6 只食蟹猴，在基线时和静脉注射 3 种不同剂量（1、2 和 4mg/kg）曲马多后，进行[11C]MADAM 和[18F]FMeNER-D2 的正电子发射断层扫描测量。估计了 5-羟色胺转运体和去甲肾上腺素转运体的剂量与占有率之间的关系。
曲马多以剂量依赖性方式相似地占据 5-羟色胺转运体（40%-72%）和去甲肾上腺素转运体（7%-73%）。5-羟色胺转运体和去甲肾上腺素转运体的 Kd 分别为 2.2mg/kg 和 2.0mg/kg。
在临床相关的高剂量曲马多作用下，脑内的 5-羟色胺转运体和去甲肾上腺素转运体被阻滞>70%。本研究表明，曲马多通过抑制脑内的 5-羟色胺转运体和去甲肾上腺素转运体具有潜在的抗抑郁作用。
