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Effect of mazindol on extracellular dopamine concentration in human brain measured by PET

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Abstract

Rationale

Mazindol, an appetite suppressant, inhibits the reuptake of dopamine in the synaptic cleft. It has been considered that mazindol might enhance dopamine transmission in the human brain. However, there has been no study that investigated the extracellular dopamine concentration in vivo.

Objective

Using positron emission tomography (PET), we aimed to measure the effect of mazindol on the extracellular dopamine concentration and to evaluate how mazindol affects the dopamine system in the healthy human brain.

Methods

Eleven healthy individuals (six males, five females, age 30.9 ± 4.9 years) were enrolled in this study. Each participant was scanned with [11C]raclopride on 1 day without any medicine as baseline condition, and on another day with mazindol as drug condition. In the drug condition, participants took mazindol 0.5 mg (N = 5) or 1.5 mg (N = 6) 2 h before the PET scan. Plasma concentrations of mazindol were measured before the injection of [11C]raclopride, and urine concentrations of mazindol were measured after the scan.

Results

After taking mazindol, the calculated decrease in binding potential (ΔBP) in the striatum was 1.74 % for 0.5 mg and 8.14 for 1.5 mg, and the correlation with the blood concentration of mazindol was significant (P = 0.0016, R 2 = 0.69). ΔBP was not significantly correlated with the urine concentration of mazindol (P = 0.84, R 2 = 0.005).

Conclusions

Mazindol increased the extracellular concentration of dopamine in the human brain, and its effect was dose dependent. A single administration of mazindol, even at usual dosage, elevated dopamine concentration similarly to other addictive drugs, suggesting that the risk of dependence may increase with the mazindol dose.

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Acknowledgments

This work was partially supported by a grant from the Ministry of Education, Culture, Sports, Science and Technology (MEXT, Japan). We thank Minoru Sakurai, Koji Nagaya, Koji Kanaya, Masaya Suda, Megumi Takei, and Kazuyoshi Honjo (Clinical Imaging Centre for Healthcare, Nippon Medical School) for their assistance in performing MRI and PET examinations.

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Authors and Affiliations

  1. Department of Neuropsychiatry, Graduate School of Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan

    Takeshi Sakayori, Amane Tateno, Ryosuke Arakawa & Yoshiro Okubo

  2. Department of Adult Mental Health, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-4-1, Ogawahigashicho, Kodaira-city, Tokyo, 187-8557, Japan

    Ryosuke Arakawa

  3. Department of Pharmacology, Graduate School of Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8602, Japan

    Yumiko Ikeda & Hidenori Suzuki

Authors
  1. Takeshi Sakayori
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  2. Amane Tateno
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  3. Ryosuke Arakawa
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  4. Yumiko Ikeda
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  5. Hidenori Suzuki
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  6. Yoshiro Okubo
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Correspondence to Yoshiro Okubo.

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Sakayori, T., Tateno, A., Arakawa, R. et al. Effect of mazindol on extracellular dopamine concentration in human brain measured by PET. Psychopharmacology 231, 2321–2325 (2014). https://doi.org/10.1007/s00213-013-3392-2

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  • DOI: https://doi.org/10.1007/s00213-013-3392-2

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