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Striatal and extrastriatal dopamine D2 receptor occupancy by the partial agonist antipsychotic drug aripiprazole in the human brain: a positron emission tomography study with [11C]raclopride and [11C]FLB457

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Abstract

Rationale

Second-generation antipsychotics demonstrate clinical efficacy with fewer extrapyramidal side effects compared with first-generation antipsychotics. One of the proposed explanations is the hypothesis of preferential extrastriatal dopamine D2 receptor occupancy (limbic selectivity) by antipsychotics. In the present study, we focused on aripiprazole, which has a unique pharmacological profile with partial agonism at dopamine D2 receptors and the minimal risk of extrapyramidal side effects. Previous positron emission tomography (PET) studies using high-affinity radioligands for dopamine D2 receptors have reported inconsistent results regarding regional differences of dopamine D2 receptor occupancy by aripiprazole.

Objective

To test the hypothesis of preferential binding to extrastriatal dopamine D2 receptors by aripiprazole, we investigated its regional dopamine D2 receptor occupancies in healthy young subjects.

Materials and methods

Using PET and two radioligands with different affinities for dopamine D2 receptors, [11C]raclopride and [11C]FLB457, striatal and extrastriatal dopamine D2 receptor bindings at baseline and after oral administration of 6 mg aripiprazole were measured in 11 male healthy subjects.

Results

Our data showed that dopamine D2 receptor occupancies in the striatum measured with [11C]raclopride were 70.1% and 74.1%, with the corresponding values for the extrastriatal regions measured with [11C]FLB457 ranging from 46.6% to 58.4%.

Conclusions

In the present study, preferential extrastriatal dopamine D2 receptor occupancy by aripiprazole was not observed. Our data suggest partial agonism at dopamine D2 receptors is the most likely explanation for the minimal risk of extrapyramidal side effects in the treatment by aripiprazole.

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Acknowledgments

This study was supported in part by a Grant-in-Aid for the Molecular Imaging Program from the Ministry of Education, Culture, Sports, Science and Technology, Japanese Government. We thank Mr. Katsuyuki Tanimoto and Mr. Takahiro Shiraishi for their assistance in performing the PET experiments, Ms. Kazuko Suzuki and Ms. Izumi Izumida for their help as clinical research coordinators, Dr. Takaaki Mori, Dr. Hajime Fukuda and Ms. Yoko Eguchi for their clinical support, and Ms. Mika Omatsu and Ms. Rie Inagaki for their help in performing MRI scanning.

Statement of interest

The authors declare that no financial support or compensation has been received from any individual or corporate entity for research or professional service, and there is no personal financial holding that could be perceived as constituting a potential conflict of interest.

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Authors and Affiliations

  1. Clinical Neuroimaging Team, Molecular Neuroimaging Program, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan

    Keisuke Takahata, Hiroshi Ito, Harumasa Takano, Ryosuke Arakawa, Hironobu Fujiwara, Yasuyuki Kimura, Fumitoshi Kodaka, Takeshi Sasaki, Tsuyoshi Nogami, Masayuki Suzuki, Tomohisa Nagashima, Hitoshi Shimada & Tetsuya Suhara

  2. Biophysics Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan

    Hiroshi Ito

  3. Department of Neuropsychiatry, Keio University, School of Medicine, Tokyo, Japan

    Keisuke Takahata, Motoichiro Kato & Masaru Mimura

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  1. Keisuke Takahata
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  2. Hiroshi Ito
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  3. Harumasa Takano
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  4. Ryosuke Arakawa
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Correspondence to Hiroshi Ito.

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Takahata, K., Ito, H., Takano, H. et al. Striatal and extrastriatal dopamine D2 receptor occupancy by the partial agonist antipsychotic drug aripiprazole in the human brain: a positron emission tomography study with [11C]raclopride and [11C]FLB457. Psychopharmacology 222, 165–172 (2012). https://doi.org/10.1007/s00213-011-2633-5

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