Comparison of Dopamine D3 and D2 Receptor Occupancies by a Single Dose of Blonanserin in Healthy Subjects: A Positron Emission Tomography Study With [11C]-(+)-PHNO
| Autor: | Yoshiro Okubo, Haruo Nakayama, Ryosuke Arakawa, Kazuyoshi Honjo, Amane Tateno, Takeshi Sakayori, WooChan Kim |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male medicine.medical_specialty positron emission tomography Dopamine Agents Substantia nigra Regular Research Articles Piperazines D3 receptor 03 medical and health sciences 0302 clinical medicine Piperidines Dopamine receptor D3 Dopamine Internal medicine Dopamine receptor D2 Oxazines medicine Humans Pharmacology (medical) Pharmacology business.industry Receptors Dopamine D2 Putamen Receptors Dopamine D3 blonanserin Blonanserin Brain Middle Aged Magnetic Resonance Imaging 030227 psychiatry D2 receptor Psychiatry and Mental health Globus pallidus Endocrinology Dopamine receptor Positron-Emission Tomography Radiopharmaceuticals business 030217 neurology & neurosurgery medicine.drug Antipsychotic Agents Protein Binding |
| Zdroj: | International Journal of Neuropsychopharmacology |
| ISSN: | 1469-5111 |
| Popis: | Background Blockade of D3 receptor, a member of the dopamine D2-like receptor family, has been suggested as a possible medication for schizophrenia. Blonanserin has high affinity in vitro for D3 as well as D2 receptors. We investigated whether a single dose of 12 mg blonanserin, which was within the daily clinical dose range (i.e., 8–24 mg) for the treatment of schizophrenia, occupies D3 as well as D2 receptors in healthy subjects. Methods Six healthy males (mean 35.7±7.6 years) received 2 positron emission tomography scans, the first prior to taking blonanserin, and the second 2 hours after the administration of a single dose of 12 mg blonanserin. Dopamine receptor occupancies by blonanserin were evaluated by [11C]-(+)-PHNO. Results Occupancy of each region by 12 mg blonanserin was: caudate (range 64.3%–81.5%; mean±SD, 74.3±5.6%), putamen (range 60.4%–84.3%; mean±SD, 73.3%±8.2%), ventral striatum (range 40.1%–88.2%; mean±SD, 60.8%±17.1%), globus pallidus (range 65.8%–87.6%; mean±SD, 75.7%±8.6%), and substantia nigra (range 56.0%–88.7%; mean±SD, 72.4%±11.0%). Correlation analysis between plasma concentration of blonanserin and receptor occupancy in D2-rich (caudate and putamen) and D3-rich (globus pallidus and substantia nigra) regions showed that EC50 for D2-rich region was 0.39 ng/mL (r=0.43) and EC50 for D3-rich region was 0.40 ng/mL (r=0.79). Conclusions A single dose of 12 mg blonanserin occupied D3 receptor to the same degree as D2 receptor in vivo. Our results were consistent with previous studies that reported that some of the pharmacological effect of blonanserin is mediated via D3 receptor antagonism. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|