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Progress in Neuro-psychopharmacology &... 19881. The use of raclopride, a new compound of the salicylamide series, as a ligand for the labelling of dopamine-D2 receptors in vitro and in vivo is described. 2.... (Review)
Review
1. The use of raclopride, a new compound of the salicylamide series, as a ligand for the labelling of dopamine-D2 receptors in vitro and in vivo is described. 2. 3H-Raclopride has a high affinity for the dopamine-D2 receptors (Kd = 1 nM in rat striatum) with much less affinity for any other receptor. 3. 3H-Raclopride enters the brain easily and has therefore also been used in in vivo binding and autoradiography. The nonspecific binding is very low both in vitro and in vivo. 4. Raclopride has been labelled with 11C, and is used as a marker for dopamine-D2 receptors in the living human brain using positron emission tomography.
Topics: Animals; Brain; Humans; Kinetics; Raclopride; Receptors, Dopamine; Receptors, Dopamine D2; Salicylamides; Tomography, Emission-Computed
PubMed: 2975809
DOI: 10.1016/0278-5846(88)90001-2 -
Current Radiopharmaceuticals 2014The dopamine D2 receptor radiotracer [(11)C]Raclopride is used extensively in clinical and preclinical imaging. Currently, a wide range of methods to produce... (Review)
Review
The dopamine D2 receptor radiotracer [(11)C]Raclopride is used extensively in clinical and preclinical imaging. Currently, a wide range of methods to produce [(11)C]Raclopride have been developed using traditional vessel reactions as well as cartridge or captive solvent. This work reports the optimisation of the production of [(11)C]Raclopride using a Synthra GPextent, comparing various methods. With optimised conditions, we were able to obtain 4±2% (ndc) yield of [(11)C]Raclopride (100 GBq [(11)C]CO2, n = 42) in 25 min. The radiochemical purity was >95% with specific activities of 135±41 MBq/nmol at end of synthesis.
Topics: Carbon Radioisotopes; Dopamine Agonists; Humans; Image Processing, Computer-Assisted; Raclopride; Radiopharmaceuticals; Receptors, Dopamine D2; Tomography, Emission-Computed
PubMed: 25335809
DOI: 10.2174/1874471007666141021111635 -
NeuroImage Feb 2020
Topics: Brain; Carbon Radioisotopes; Humans; Raclopride; Reproducibility of Results
PubMed: 31715255
DOI: 10.1016/j.neuroimage.2019.116346 -
European Neuropsychopharmacology : the... May 2023
Topics: Humans; Raclopride; Fluorodeoxyglucose F18; Positron-Emission Tomography; Neuroimaging; Occupational Stress; Radiopharmaceuticals
PubMed: 36857874
DOI: 10.1016/j.euroneuro.2023.02.013 -
NeuroImage Feb 2020
Topics: Brain; Carbon Radioisotopes; Humans; Raclopride; Reproducibility of Results
PubMed: 31756518
DOI: 10.1016/j.neuroimage.2019.116371 -
Psychopharmacology Series 1989
Review
Topics: Animals; Behavior, Animal; Biogenic Monoamines; Dopamine Antagonists; Humans; Raclopride; Receptors, Dopamine; Salicylamides
PubMed: 2687851
DOI: 10.1007/978-3-642-74430-3_13 -
Molecular Imaging and Biology 2005Measuring changes in dopamine (DA) levels in humans using radioligand-displacement studies and positron emission tomography (PET) has provided important empirical... (Review)
Review
Measuring changes in dopamine (DA) levels in humans using radioligand-displacement studies and positron emission tomography (PET) has provided important empirical findings in diseases and normal neurophysiology. These studies are based on the assumption that DA exerts a competitive inhibition on D(2)-radioligand binding. However, the transfer of this hypothesis to a proven mechanism has not been fully achieved yet and an accumulating number of studies challenge it. In addition, new evidence suggests that DA exerts a noncompetitive inhibition on D(2)-radioligand binding under amphetamine conditions. This article reviews the theoretical basis for the DA competition hypothesis, the in vivo and in vitro evidences supporting a noncompetitive action of DA on D(2)-radioligand binding under amphetamine conditions, and discusses possible mechanisms underlying this noncompetitive interaction. Finally, we propose that such noncompetitive interactions may have important implications for how one interprets findings obtained from radioligand-displacement PET studies in neuropsychiatric diseases, especially in schizophrenia in which a dysregulation of the DA-promoted internalization of D(2) receptors was recently suggested.
Topics: Animals; Carbon Radioisotopes; Dopamine; Dopamine Agonists; Humans; Models, Biological; Raclopride; Receptors, Dopamine
PubMed: 15912275
DOI: 10.1007/s11307-005-0932-0 -
Scientific Reports Jul 2022The dopamine blockade by antipsychotics trigger subjective dysphoria. Compared with D2 antagonists, aripiprazole, a D2 partial agonist, was expected to produce a...
The dopamine blockade by antipsychotics trigger subjective dysphoria. Compared with D2 antagonists, aripiprazole, a D2 partial agonist, was expected to produce a different experience. Indeed, a previous study reported no relationship between the D2 receptor occupancy by aripiprazole and subjective dysphoria, while the D2 receptor occupancy by antagonists was associated with negative subjective experiences. This study revisited the relationship in patients treated with aripiprazole by using an inhibitory E model, which enables the individual drug-free binding potential and D2 receptor occupancy to be properly estimated. Eight patients with schizophrenia who have been clinically stable on aripiprazole were enrolled. Assessments including Positive and Negative Syndrome Scale (PANSS) and Subjective Well-being under Neuroleptics Scale (Kv-SWN) were administered. [C]raclopride PET scan were conducted 2, 26, and 74 h after aripiprazole administration. Regression analysis showed a significant negative association between the D2 receptor occupancy by aripiprazole in the striatum and the Kv-SWN (R = 0.55, p = 0.036), but the PANSS total score was not associated with the Kv-SWN (R = 0.42, p = 0.080). The negative association between D2 receptor occupancy by aripiprazole and subjective well-being implies that clinicians should find the lowest effective doses of aripiprazole for clinically stable patients to improve their subjective experiences and clinical outcomes.
Topics: Antipsychotic Agents; Aripiprazole; Humans; Positron-Emission Tomography; Raclopride; Receptors, Dopamine D2
PubMed: 35840763
DOI: 10.1038/s41598-022-16130-5 -
Psychiatry Research. Neuroimaging Aug 2023Anhedonia is hypothesized to be associated with blunted mesocorticolimbic dopamine (DA) functioning in samples with major depressive disorder. The purpose of this study...
BACKGROUND
Anhedonia is hypothesized to be associated with blunted mesocorticolimbic dopamine (DA) functioning in samples with major depressive disorder. The purpose of this study was to examine linkages between striatal DA, reward circuitry functioning, anhedonia, and, in an exploratory fashion, self-reported stress, in a transdiagnostic anhedonic sample.
METHODS
Participants with (n = 25) and without (n = 12) clinically impairing anhedonia completed a reward-processing task during simultaneous positron emission tomography and magnetic resonance (PET-MR) imaging with [C]raclopride, a DA D2/D3 receptor antagonist that selectively binds to striatal DA receptors.
RESULTS
Relative to controls, the anhedonia group exhibited decreased task-related DA release in the left putamen, caudate, and nucleus accumbens and right putamen and pallidum. There were no group differences in task-related brain activation (fMRI) during reward processing after correcting for multiple comparisons. General functional connectivity (GFC) findings revealed blunted fMRI connectivity between PET-derived striatal seeds and target regions in the anhedonia group. Associations were identified between anhedonia severity and the magnitude of task-related DA release to rewards in the left putamen, but not mesocorticolimbic GFC.
CONCLUSIONS
Results provide evidence for reduced striatal DA functioning during reward processing and blunted mesocorticolimbic network functional connectivity in a transdiagnostic sample with clinically significant anhedonia.
Topics: Humans; Raclopride; Dopamine; Anhedonia; Depressive Disorder, Major; Positron-Emission Tomography; Magnetic Resonance Imaging
PubMed: 37301129
DOI: 10.1016/j.pscychresns.2023.111660 -
Psychiatry and Clinical Neurosciences Apr 2020The aim of the study was to test: (i) if D /D binding in three functional subsections of striatum is different in patients with severe major depressive episodes than in...
[ C]raclopride positron emission tomography study of dopamine-D receptor binding in patients with severe major depressive episodes before and after electroconvulsive therapy and compared to control subjects.
AIM
The aim of the study was to test: (i) if D /D binding in three functional subsections of striatum is different in patients with severe major depressive episodes than in controls; and (ii) if this difference is normalized after electroconvulsive therapy (ECT).
METHODS
Nine inpatients were examined with positron emission tomography (PET) and the radioligand [ C]raclopride before and after an average of 8.4 ECT sessions. Treatment response was assessed using the Montgomery-Åsberg Depression Rating Scale. Nine age- and sex-matched controls were examined twice with PET and [ C]raclopride.
RESULTS
[ C]raclopride binding was significantly lower in all three subsections of striatum in patients compared to controls (Cohen's d , 1.14-1.68; P = 0.003-0.027). Montgomery-Åsberg Depression Ratings decreased significantly after ECT (P < 0.001; Cohen's d , 2.9). ECT had no statistically significant effect on [ C]raclopride binding, although post-ECT binding estimates were more similar to those obtained in controls in all subsections of striatum.
CONCLUSION
Using PET and [ C]raclopride, we found support for the notion that severe major depressive episodes are associated with significantly lower dopamine D /D binding in all three subsections of striatum compared to controls. We noted no significant effect on D /D binding in the patient group after response to ECT.
Topics: Adult; Aged; Brain Mapping; Carbon Radioisotopes; Corpus Striatum; Depressive Disorder, Major; Dopamine; Dopamine Antagonists; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Positron-Emission Tomography; Protein Binding; Raclopride; Receptors, Dopamine D2; Receptors, Dopamine D3
PubMed: 31943514
DOI: 10.1111/pcn.12980