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Positron emission tomography measurement of dopamine D₂ receptor occupancy in the pituitary and cerebral cortex: relation to antipsychotic-induced hyperprolactinemia.
J Clin Psychiatry. 2010 Sep; 71(9):1131-7.JC

Abstract

OBJECTIVE

Hyperprolactinemia is a common side effect of antipsychotic drugs used in the treatment of schizophrenia. However, the magnitude of hyperprolactinemia differs among antipsychotics, and there is no reliable mechanism-related marker for the risk of hyperprolactinemia that would allow us to characterize antipsychotics.

METHOD

In this study, 11 healthy male subjects taking different doses of sulpiride and 24 male patients with DSM-IV-diagnosed schizophrenia taking different antipsychotic drugs (risperidone, olanzapine, haloperidol, and sulpiride) participated. Positron emission tomography scanning using [¹¹C]FLB 457 was performed on all subjects. The dopamine D₂receptor occupancy of antipsychotics in the pituitary and temporal cortex was calculated. Correlations between plasma concentration of prolactin and dopamine D₂receptor occupancies were evaluated. The ratio of drug concentration of cerebral receptor site to that of pituitary receptor site (brain/plasma concentration ratio; B/P ratio) was calculated from the receptor occupancies in the 2 regions. Data were collected between November 2001 and September 2007.

RESULTS

Significant positive correlation was observed between the plasma concentration of prolactin and dopamine D₂receptor occupancy in the pituitary by all 4 antipsychotics (P = .001). Dopamine D₂receptor occupancies of sulpiride were markedly different between the pituitary and temporal cortex, and the B/P ratio for sulpiride (0.34) was significantly lower than for olanzapine (P = .007) and risperidone (P = .015). Olanzapine had a relatively high B/P ratio (2.70), followed by haloperidol (2.40) and risperidone (1.61).

CONCLUSIONS

Dopamine D₂receptor occupancy in the pituitary is a good indicator of hyperprolactinemia. B/P ratio, indicating the penetrating capability across the blood-brain barrier, seems to be a good characteristic biomarker of each antipsychotic drug for the risk of hyperprolactinemia at therapeutic dose.

Authors+Show Affiliations

Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Inage-ku, Chiba, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20361897

Citation

Arakawa, Ryosuke, et al. "Positron Emission Tomography Measurement of Dopamine D₂ Receptor Occupancy in the Pituitary and Cerebral Cortex: Relation to Antipsychotic-induced Hyperprolactinemia." The Journal of Clinical Psychiatry, vol. 71, no. 9, 2010, pp. 1131-7.
Arakawa R, Okumura M, Ito H, et al. Positron emission tomography measurement of dopamine D₂ receptor occupancy in the pituitary and cerebral cortex: relation to antipsychotic-induced hyperprolactinemia. J Clin Psychiatry. 2010;71(9):1131-7.
Arakawa, R., Okumura, M., Ito, H., Takano, A., Takahashi, H., Takano, H., Maeda, J., Okubo, Y., & Suhara, T. (2010). Positron emission tomography measurement of dopamine D₂ receptor occupancy in the pituitary and cerebral cortex: relation to antipsychotic-induced hyperprolactinemia. The Journal of Clinical Psychiatry, 71(9), 1131-7. https://doi.org/10.4088/JCP.08m04307yel
Arakawa R, et al. Positron Emission Tomography Measurement of Dopamine D₂ Receptor Occupancy in the Pituitary and Cerebral Cortex: Relation to Antipsychotic-induced Hyperprolactinemia. J Clin Psychiatry. 2010;71(9):1131-7. PubMed PMID: 20361897.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Positron emission tomography measurement of dopamine D₂ receptor occupancy in the pituitary and cerebral cortex: relation to antipsychotic-induced hyperprolactinemia. AU - Arakawa,Ryosuke, AU - Okumura,Masaki, AU - Ito,Hiroshi, AU - Takano,Akihiro, AU - Takahashi,Hidehiko, AU - Takano,Harumasa, AU - Maeda,Jun, AU - Okubo,Yoshiro, AU - Suhara,Tetsuya, Y1 - 2010/02/23/ PY - 2008/04/17/received PY - 2009/04/15/accepted PY - 2010/4/6/entrez PY - 2010/4/7/pubmed PY - 2010/10/23/medline SP - 1131 EP - 7 JF - The Journal of clinical psychiatry JO - J Clin Psychiatry VL - 71 IS - 9 N2 - OBJECTIVE: Hyperprolactinemia is a common side effect of antipsychotic drugs used in the treatment of schizophrenia. However, the magnitude of hyperprolactinemia differs among antipsychotics, and there is no reliable mechanism-related marker for the risk of hyperprolactinemia that would allow us to characterize antipsychotics. METHOD: In this study, 11 healthy male subjects taking different doses of sulpiride and 24 male patients with DSM-IV-diagnosed schizophrenia taking different antipsychotic drugs (risperidone, olanzapine, haloperidol, and sulpiride) participated. Positron emission tomography scanning using [¹¹C]FLB 457 was performed on all subjects. The dopamine D₂receptor occupancy of antipsychotics in the pituitary and temporal cortex was calculated. Correlations between plasma concentration of prolactin and dopamine D₂receptor occupancies were evaluated. The ratio of drug concentration of cerebral receptor site to that of pituitary receptor site (brain/plasma concentration ratio; B/P ratio) was calculated from the receptor occupancies in the 2 regions. Data were collected between November 2001 and September 2007. RESULTS: Significant positive correlation was observed between the plasma concentration of prolactin and dopamine D₂receptor occupancy in the pituitary by all 4 antipsychotics (P = .001). Dopamine D₂receptor occupancies of sulpiride were markedly different between the pituitary and temporal cortex, and the B/P ratio for sulpiride (0.34) was significantly lower than for olanzapine (P = .007) and risperidone (P = .015). Olanzapine had a relatively high B/P ratio (2.70), followed by haloperidol (2.40) and risperidone (1.61). CONCLUSIONS: Dopamine D₂receptor occupancy in the pituitary is a good indicator of hyperprolactinemia. B/P ratio, indicating the penetrating capability across the blood-brain barrier, seems to be a good characteristic biomarker of each antipsychotic drug for the risk of hyperprolactinemia at therapeutic dose. SN - 1555-2101 UR - https://www.unboundmedicine.com/medline/citation/20361897/Positron_emission_tomography_measurement_of_dopamine_D₂_receptor_occupancy_in_the_pituitary_and_cerebral_cortex:_relation_to_antipsychotic_induced_hyperprolactinemia_ L2 - http://www.psychiatrist.com/jcp/article/pages/2010/v71n09/v71n0904.aspx DB - PRIME DP - Unbound Medicine ER -