Effect of risperidone on high-affinity state of dopamine D2 receptors: a PET study with agonist ligand 11C(R)-2-CH3O-N-n-propylnorapomorphine.
Summary of "Effect of risperidone on high-affinity state of dopamine D2 receptors: a PET study with agonist ligand 11C(R)-2-CH3O-N-n-propylnorapomorphine."
The increased proportion of the high-affinity state of dopamine D2/3 receptors (D2,high) is assumed to correlate with dopamine hypersensitivity, implying a relationship with psychotic symptoms observed in psychiatric disorders such as schizophrenia. [11C](R)-2-CH3O-N-n-propylnorapomorphine ([11C]MNPA), which has an agonistic property to dopamine D2 receptors (D2Rs), is expected to bind preferentially to D2,high. The occupancy of dopamine D2Rs by antagonists to receptors has not been investigated using [11C]MNPA. We compared dopamine D2R occupancies by risperidone, an antagonist to receptors, between [11C]MNPA and [11C]raclopride to confirm whether risperidone occupies D2,high and D2,low at almost identical proportions. PET studies were performed on 11 healthy men under resting condition and following oral administration of a single dose of risperidone (0.5-2.0 mg). Striatal receptor occupancy for each radioligand was calculated. The relationship between dose or plasma concentration of risperidone and dopamine D2R occupancy was calculated. Striatal dopamine D2R occupancies measured with [11C]MNPA and [11C]raclopride were 22-65% and 24-69%, respectively. In the striatum, ED50 values measured with [11C]MNPA and [11C]raclopride were 0.98 and 1.03 mg, respectively. The striatal ED50 values as calculated from plasma concentration were 9.15 ng/ml and 8.01 ng/ml, respectively. Almost identical occupancies and ED50 values were observed between the two radioligands, indicating that risperidone bound to D2,high and D2,low at almost identical proportions in a dose-dependent manner.
Affiliation
Clinical Neuroimaging Team, Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
Journal Details
This article was published in the following journal.
Name: The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychoph
ISSN: 1469-5111
Pages: 1-7
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20860881
- DOI: http://dx.doi.org/10.1017/S1461145710001148
Medical and Biotech [MESH] Definitions
Receptors, Dopamine D4
A subtype of dopamine D2 receptors that has high affinity for the antipsychotic CLOZAPINE.
Receptors, Dopamine
Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells.
Receptors, Dopamine D5
A subtype of dopamine D1 receptors that has higher affinity for DOPAMINE and differentially couples to GTP-BINDING PROTEINS.
Risperidone
A selective blocker of DOPAMINE D2 RECEPTORS and SEROTONIN 5-HT2 RECEPTORS that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of SCHIZOPHRENIA.
Dopamine Plasma Membrane Transport Proteins
Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of dopaminergic neurons. They remove DOPAMINE from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS and are the target of DOPAMINE UPTAKE INHIBITORS.
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