Occupancy of Norepinephrine Transporter by Duloxetine in Human Brains Measured by Positron Emission Tomography with (S,S)-[18F]FMeNER-D2

Sho Moriguchi, Harumasa Takano, Yasuyuki Kimura, Tomohisa Nagashima, Keisuke Takahata, Manabu Kubota, Soichiro Kitamura, Tatsuya Ishii, Masanori Ichise, Ming Rong Zhang, Hitoshi Shimada, Masaru Mimura, Jeffrey H. Meyer, Makoto Higuchi, Tetsuya Suhara

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: The norepinephrine transporter in the brain has been targeted in the treatment of psychiatric disorders. Duloxetine is a serotonin and norepinephrine reuptake inhibitor that has been widely used for the treatment of depression. However, the relationship between dose and plasma concentration of duloxetine and norepinephrine transporter occupancy in the human brain has not been determined. In this study, we examined norepinephrine transporter occupancy by different doses of duloxetine.

Methods: We calculated norepinephrine transporter occupancies from 2 positron emission tomography scans using (S,S)-[18F]FMeNER-D2 before and after a single oral dose of duloxetine (20 mg, n = 3; 40 mg, n = 3; 60 mg, n =2). Positron emission tomography scans were performed from 120 to 180 minutes after an i.v. bolus injection of (S,S)-[18F]FMeNER-D2. Venous blood samples were taken to measure the plasma concentration of duloxetine just before and after the second positron emission tomography scan.

Results: Norepinephrine transporter occupancy by duloxetine was 29.7% at 20 mg, 30.5% at 40 mg, and 40.0% at 60 mg. The estimated dose of duloxetine inducing 50% norepinephrine transporter occupancy was 76.8 mg, and the estimated plasma drug concentration inducing 50% norepinephrine transporter occupancy was 58.0 ng/mL.

Conclusions: Norepinephrine transporter occupancy by clinical doses of duloxetine was approximately 30% to 40% in human brain as estimated using positron emission tomography with (S,S)-[18F]FMeNER-D2.

Original languageEnglish
Pages (from-to)957-962
Number of pages6
JournalThe international journal of neuropsychopharmacology
Volume20
Issue number12
DOIs
Publication statusPublished - 2017 Dec 1

Fingerprint

Norepinephrine Plasma Membrane Transport Proteins
Positron-Emission Tomography
Brain
Duloxetine Hydrochloride
2-(alpha-(2-fluoromethoxyphenoxy)benzyl)morpholine
Psychiatry
Injections

Keywords

  • (S,S)-[18F]FMeNER-D2
  • duloxetine
  • norepinephrine transporter
  • occupancy
  • PET

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Occupancy of Norepinephrine Transporter by Duloxetine in Human Brains Measured by Positron Emission Tomography with (S,S)-[18F]FMeNER-D2. / Moriguchi, Sho; Takano, Harumasa; Kimura, Yasuyuki; Nagashima, Tomohisa; Takahata, Keisuke; Kubota, Manabu; Kitamura, Soichiro; Ishii, Tatsuya; Ichise, Masanori; Zhang, Ming Rong; Shimada, Hitoshi; Mimura, Masaru; Meyer, Jeffrey H.; Higuchi, Makoto; Suhara, Tetsuya.

In: The international journal of neuropsychopharmacology, Vol. 20, No. 12, 01.12.2017, p. 957-962.

Research output: Contribution to journalArticle

Moriguchi, S, Takano, H, Kimura, Y, Nagashima, T, Takahata, K, Kubota, M, Kitamura, S, Ishii, T, Ichise, M, Zhang, MR, Shimada, H, Mimura, M, Meyer, JH, Higuchi, M & Suhara, T 2017, 'Occupancy of Norepinephrine Transporter by Duloxetine in Human Brains Measured by Positron Emission Tomography with (S,S)-[18F]FMeNER-D2', The international journal of neuropsychopharmacology, vol. 20, no. 12, pp. 957-962. https://doi.org/10.1093/ijnp/pyx069
Moriguchi, Sho ; Takano, Harumasa ; Kimura, Yasuyuki ; Nagashima, Tomohisa ; Takahata, Keisuke ; Kubota, Manabu ; Kitamura, Soichiro ; Ishii, Tatsuya ; Ichise, Masanori ; Zhang, Ming Rong ; Shimada, Hitoshi ; Mimura, Masaru ; Meyer, Jeffrey H. ; Higuchi, Makoto ; Suhara, Tetsuya. / Occupancy of Norepinephrine Transporter by Duloxetine in Human Brains Measured by Positron Emission Tomography with (S,S)-[18F]FMeNER-D2. In: The international journal of neuropsychopharmacology. 2017 ; Vol. 20, No. 12. pp. 957-962.
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abstract = "Background: The norepinephrine transporter in the brain has been targeted in the treatment of psychiatric disorders. Duloxetine is a serotonin and norepinephrine reuptake inhibitor that has been widely used for the treatment of depression. However, the relationship between dose and plasma concentration of duloxetine and norepinephrine transporter occupancy in the human brain has not been determined. In this study, we examined norepinephrine transporter occupancy by different doses of duloxetine.Methods: We calculated norepinephrine transporter occupancies from 2 positron emission tomography scans using (S,S)-[18F]FMeNER-D2 before and after a single oral dose of duloxetine (20 mg, n = 3; 40 mg, n = 3; 60 mg, n =2). Positron emission tomography scans were performed from 120 to 180 minutes after an i.v. bolus injection of (S,S)-[18F]FMeNER-D2. Venous blood samples were taken to measure the plasma concentration of duloxetine just before and after the second positron emission tomography scan.Results: Norepinephrine transporter occupancy by duloxetine was 29.7{\%} at 20 mg, 30.5{\%} at 40 mg, and 40.0{\%} at 60 mg. The estimated dose of duloxetine inducing 50{\%} norepinephrine transporter occupancy was 76.8 mg, and the estimated plasma drug concentration inducing 50{\%} norepinephrine transporter occupancy was 58.0 ng/mL.Conclusions: Norepinephrine transporter occupancy by clinical doses of duloxetine was approximately 30{\%} to 40{\%} in human brain as estimated using positron emission tomography with (S,S)-[18F]FMeNER-D2.",
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AU - Takano, Harumasa

AU - Kimura, Yasuyuki

AU - Nagashima, Tomohisa

AU - Takahata, Keisuke

AU - Kubota, Manabu

AU - Kitamura, Soichiro

AU - Ishii, Tatsuya

AU - Ichise, Masanori

AU - Zhang, Ming Rong

AU - Shimada, Hitoshi

AU - Mimura, Masaru

AU - Meyer, Jeffrey H.

AU - Higuchi, Makoto

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N2 - Background: The norepinephrine transporter in the brain has been targeted in the treatment of psychiatric disorders. Duloxetine is a serotonin and norepinephrine reuptake inhibitor that has been widely used for the treatment of depression. However, the relationship between dose and plasma concentration of duloxetine and norepinephrine transporter occupancy in the human brain has not been determined. In this study, we examined norepinephrine transporter occupancy by different doses of duloxetine.Methods: We calculated norepinephrine transporter occupancies from 2 positron emission tomography scans using (S,S)-[18F]FMeNER-D2 before and after a single oral dose of duloxetine (20 mg, n = 3; 40 mg, n = 3; 60 mg, n =2). Positron emission tomography scans were performed from 120 to 180 minutes after an i.v. bolus injection of (S,S)-[18F]FMeNER-D2. Venous blood samples were taken to measure the plasma concentration of duloxetine just before and after the second positron emission tomography scan.Results: Norepinephrine transporter occupancy by duloxetine was 29.7% at 20 mg, 30.5% at 40 mg, and 40.0% at 60 mg. The estimated dose of duloxetine inducing 50% norepinephrine transporter occupancy was 76.8 mg, and the estimated plasma drug concentration inducing 50% norepinephrine transporter occupancy was 58.0 ng/mL.Conclusions: Norepinephrine transporter occupancy by clinical doses of duloxetine was approximately 30% to 40% in human brain as estimated using positron emission tomography with (S,S)-[18F]FMeNER-D2.

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