Nogami Tsuyoshi, Arakawa Ryosuke, Sakayori Takeshi, Ikeda Yumiko, Okubo Yoshiro, Tateno Amane
Department of Neuropsychiatry, Nippon Medical School, Tokyo, Japan.
Department of Pharmacology, Nippon Medical School, Tokyo, Japan.
Front Psychiatry. 2022 May 31;13:799319. doi: 10.3389/fpsyt.2022.799319. eCollection 2022.
Since ephedrine has a dopamine transporter (DAT) inhibitory effect similar to amphetamine, dl-methylephedrine, a derivative of ephedrine, is considered to have the characteristics of a central nervous system stimulant due to the DAT inhibitory effect. For example, the World Anti-Doping Agency categorizes dl-methylephedrine as a stimulant in the prohibited list for competitions. Assuming to have the same effect as ephedrine, the urinary concentration of dl-methylephedrine is regulated below 10 μg/mL, as is ephedrine. However, the extent to which dl-methylephedrine affects brain function is not yet fully understood.
The purpose of this study was to evaluate DAT occupancy by a single oral administration of a daily dose of dl-methylephedrine using positron emission tomography (PET) with [F]FE-PE2I to characterize its stimulatory effect on the central nervous system.
Nine healthy male volunteers were enrolled in the study. The experiments were designed as a placebo-controlled randomized double-blind crossover comparative study. After the first PET scan in a drug-free state, the second and third PET scans were performed with randomized dosing at 60 mg of dl-methylephedrine or placebo. The plasma and urine concentrations of dl-methylephedrine were measured just before and after the PET scans, respectively.
Mean urine and plasma concentrations of dl-methylephedrine were 13.9 μg/mL and 215.2 ng/mL, respectively. Mean DAT occupancy in the caudate was 4.4% for dl-methylephedrine and 1.2% for placebo. Mean DAT occupancy in the putamen was 3.6% for dl-methylephedrine and 0.5% for placebo. There was no significant difference of DAT occupancies between the groups.
In this study, the urinary concentration of dl-methylephedrine (13.9 μg/mL) was higher than the prohibited reference value (10.0 μg/mL), and there was no significant difference in DAT occupancy between dl-methylephedrine and placebo. These findings suggest that a clinical daily dose of dl-methylephedrine may exceed the doping regulation value according to urine concentration; however, it was considered that at least the central excitatory effect mediated by DAT inhibition was not observed at the daily dose of dl-methylephedrine.
由于麻黄碱具有与苯丙胺类似的多巴胺转运体（DAT）抑制作用，麻黄碱的衍生物消旋甲基麻黄碱因DAT抑制作用而被认为具有中枢神经系统兴奋剂的特征。例如，世界反兴奋剂机构将消旋甲基麻黄碱列入比赛禁用清单中的兴奋剂类别。假设其与麻黄碱具有相同的作用，消旋甲基麻黄碱的尿浓度与麻黄碱一样被规定在10μg/mL以下。然而，消旋甲基麻黄碱对脑功能的影响程度尚未完全明确。
本研究的目的是使用[F]FE-PE2I正电子发射断层扫描（PET）评估每日单次口服一剂消旋甲基麻黄碱后的DAT占有率，以表征其对中枢神经系统的刺激作用。
9名健康男性志愿者参与了本研究。实验设计为安慰剂对照随机双盲交叉比较研究。在无药状态下进行首次PET扫描后，分别以60mg消旋甲基麻黄碱或安慰剂随机给药进行第二次和第三次PET扫描。在PET扫描前后分别测量消旋甲基麻黄碱的血浆和尿液浓度。
消旋甲基麻黄碱的平均尿液和血浆浓度分别为13.9μg/mL和215.2ng/mL。消旋甲基麻黄碱组尾状核的平均DAT占有率为4.4%，安慰剂组为1.2%。消旋甲基麻黄碱组壳核的平均DAT占有率为3.6%，安慰剂组为0.5%。两组之间的DAT占有率无显著差异。
在本研究中，消旋甲基麻黄碱的尿浓度（13.9μg/mL）高于禁用参考值（10.0μg/mL），且消旋甲基麻黄碱与安慰剂之间的DAT占有率无显著差异。这些发现表明，消旋甲基麻黄碱的临床日剂量根据尿液浓度可能超过兴奋剂管制值；然而，据认为在消旋甲基麻黄碱的日剂量下至少未观察到由DAT抑制介导的中枢兴奋作用。
