使用正电子发射断层扫描研究曲马多在非人灵长类动物中的血清素和去甲肾上腺素转运体占有率。
Serotonin and Norepinephrine Transporter Occupancy of Tramadol in Nonhuman Primate Using Positron Emission Tomography.
机构信息
Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet and Stockholm County Council, Stockholm, Sweden.
出版信息
Int J Neuropsychopharmacol. 2019 Jan 1;22(1):53-56. doi: 10.1093/ijnp/pyy089.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
背景
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。
方法
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。
结果
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。
结论
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。
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