Takano Harumasa, Arakawa Ryosuke, Nogami Tsuyoshi, Suzuki Masayuki, Nagashima Tomohisa, Fujiwara Hironobu, Kimura Yasuyuki, Kodaka Fumitoshi, Takahata Keisuke, Shimada Hitoshi, Murakami Yoshitaka, Tateno Amane, Yamada Makiko, Ito Hiroshi, Kawamura Kazunori, Zhang Ming-Rong, Takahashi Hidehiko, Kato Motoichiro, Okubo Yoshiro, Suhara Tetsuya
Clinical Neuroimaging Team, Molecular Neuroimaging Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
Department of Medical Statistics, Shiga University of Medical Science, Shiga, Japan.
Int J Neuropsychopharmacol. 2014 Apr;17(4):553-60. doi: 10.1017/S1461145713001521. Epub 2013 Dec 18.
Norepinephrine transporter (NET) plays important roles in the treatment of various neuropsychiatric disorders, such as depression and attention deficit hyperactivity disorder (ADHD). Nortriptyline is a NET-selective tricyclic antidepressant (TCAs) that has been widely used for the treatment of depression. Previous positron emission tomography (PET) studies have reported over 80% serotonin transporter occupancy with clinical doses of selective serotonin reuptake inhibitors (SSRIs), but there has been no report of NET occupancy in patients treated with relatively NET-selective antidepressants. In the present study, we used PET and (S,S)-[18¹⁸F]FMeNER-D₂ to investigate NET occupancies in the thalamus in 10 patients with major depressive disorder taking various doses of nortriptyline, who were considered to be responders to the treatment. Reference data for the calculation of occupancy were derived from age-matched healthy controls. The result showed approximately 50-70% NET occupancies in the brain as a result of the administration of 75-200 mg/d of nortriptyline. The estimated effective dose (ED₅₀) and concentration (EC₅₀) required to induce 50% occupancy was 65.9 mg/d and 79.8 ng/ml, respectively. Furthermore, as the minimum therapeutic level of plasma nortriptyline for the treatment of depression has been reported to be 70 ng/ml, our data indicate that this plasma nortriptyline concentration corresponds to approximately 50% NET occupancy measured with PET, suggesting that more than 50% of central NET occupancy would be appropriate for the nortriptyline treatment of patients with depression.
去甲肾上腺素转运体（NET）在治疗各种神经精神疾病中发挥着重要作用，如抑郁症和注意力缺陷多动障碍（ADHD）。去甲替林是一种NET选择性三环类抗抑郁药（TCAs），已被广泛用于治疗抑郁症。先前的正电子发射断层扫描（PET）研究报告称，临床剂量的选择性5-羟色胺再摄取抑制剂（SSRIs）可使5-羟色胺转运体占有率超过80%，但尚未有关于使用相对NET选择性抗抑郁药治疗的患者中NET占有率的报告。在本研究中，我们使用PET和（S,S）-[¹⁸F]FMeNER-D₂来研究10例服用不同剂量去甲替林且被认为对治疗有反应的重度抑郁症患者丘脑的NET占有率。计算占有率的参考数据来自年龄匹配的健康对照。结果显示，服用75-200mg/d去甲替林后，大脑中的NET占有率约为50-70%。诱导50%占有率所需的估计有效剂量（ED₅₀）和浓度（EC₅₀）分别为65.9mg/d和79.8ng/ml。此外，由于据报道治疗抑郁症的血浆去甲替林最低治疗水平为70ng/ml，我们的数据表明，这种血浆去甲替林浓度对应于PET测量的约50%的NET占有率，这表明超过50%的中枢NET占有率可能适合去甲替林治疗抑郁症患者。
