Raclopride

Patterns of age related changes for phosphodiesterase type-10A in comparison with dopamine D2/3 receptors and sub-cortical volumes in the human basal ganglia: A PET study with (18)F-MNI-659 and (11)C-raclopride with correction for partial volume effect.[Pubmed:28254508]

Neuroimage. 2017 May 15;152:330-339.

Phosphodiesterase 10A enzyme (PDE10A) is an important striatal target that has been shown to be affected in patients with neurodegenerative disorders, particularly Huntington s disease (HD). PDE10A is expressed on striatal neurones in basal ganglia where other known molecular targets are enriched such as dopamine D2/3 receptors (D2/3 R). The aim of this study was to examine the availability of PDE10A enzyme in relation with age and gender and to compare those changes with those related to D2/3 R and volumes in different regions of the basal ganglia. As a secondary objective we examined the relative distribution of D2/3 R and PDE10A enzyme in the striatum and globus pallidus. Forty control subjects (20F/20M; age: 44+/-11y, age range 27-69) from an ongoing positron emission tomography (PET) study in HD gene expansion carriers were included. Subjects were examined with PET using the high-resolution research tomograph (HRRT) and with 3T magnetic resonance imaging (MRI). The PDE10A radioligand (18)F-MNI-659 and D2/3 R radioligand (11)C-Raclopride were used. The outcome measure was the binding potential (BPND) estimated with the two-tissue compartment model ((18)F-MNI-659) and the simplified reference tissue model ((11)C-Raclopride) using the cerebellum as reference region. The PET data were corrected for partial volume effects. In the striatum, PDE10A availability showed a significant age-related decline that was larger compared to the age-related decline of D2/3 R availability and to the age-related decline of volumes measured with MRI. In the globus pallidus, a less pronounced decline of PDE10A availability was observed, whereas D2/3 R availability and volumes seemed to be rather stable with aging. The distribution of the PDE10A enzyme was different from the distribution of D2/3 R, with higher availability in the globus pallidus. These results indicate that aging is associated with a considerable physiological reduction of the availability of PDE10A enzyme in the striatum. Moreover as result of the analysis, in the striatum for both the molecular targets, we observed a gender effect with higher BPND the female group.

Comparison of manual and automatic techniques for substriatal segmentation in 11C-raclopride high-resolution PET studies.[Pubmed:27286237]

Nucl Med Commun. 2016 Oct;37(10):1074-87.

BACKGROUND: The striatum is the primary target in regional C-Raclopride-PET studies, and despite its small volume, it contains several functional and anatomical subregions. The outcome of the quantitative dopamine receptor study using C-Raclopride-PET depends heavily on the quality of the region-of-interest (ROI) definition of these subregions. The aim of this study was to evaluate subregional analysis techniques because new approaches have emerged, but have not yet been compared directly. MATERIALS AND METHODS: In this paper, we compared manual ROI delineation with several automatic methods. The automatic methods used either direct clustering of the PET image or individualization of chosen brain atlases on the basis of MRI or PET image normalization. State-of-the-art normalization methods and atlases were applied, including those provided in the FreeSurfer, Statistical Parametric Mapping8, and FSL software packages. Evaluation of the automatic methods was based on voxel-wise congruity with the manual delineations and the test-retest variability and reliability of the outcome measures using data from seven healthy male participants who were scanned twice with C-Raclopride-PET on the same day. RESULTS: The results show that both manual and automatic methods can be used to define striatal subregions. Although most of the methods performed well with respect to the test-retest variability and reliability of binding potential, the smallest average test-retest variability and SEM were obtained using a connectivity-based atlas and PET normalization (test-retest variability=4.5%, SEM=0.17). CONCLUSION: The current state-of-the-art automatic ROI methods can be considered good alternatives for subjective and laborious manual segmentation in C-Raclopride-PET studies.

Successful application of a neutral organic base, 1,8-bis(tetramethylguanidino)naphthalene (TMGN), for the radiosynthesis of [(11)C]raclopride.[Pubmed:27894050]

Appl Radiat Isot. 2016 Dec;118:382-388.

[(11)C]Raclopride is one of the most popular PET tracers used in Parkinson's disease studies. We previously prepared [(11)C]Raclopride with reasonable yields using NaOH as an inorganic base, but the reaction patterns fluctuated. In this study, we describe the successful application of a commercially available 'super basic' proton sponge, TMGN, as a base for the [(11)C]methylation step using [(11)C]CH3OTf. This novel TMGN method produced better radiochemical yields, as well as enhanced reproducibility and a reduction in side products. Under optimal conditions (1.2 equiv. of TMGN), the radiochemical yield was 14.4+/-0.2% (ndc, EOS, n=5) and the specific activity was 66.6+/-13.3 GBq/mmol (n=5).

Corticostriatal and Dopaminergic Response to Beer Flavor with Both fMRI and [(11) C]raclopride Positron Emission Tomography.[Pubmed:27459715]

Alcohol Clin Exp Res. 2016 Sep;40(9):1865-73.

BACKGROUND: Cue-evoked drug-seeking behavior likely depends on interactions between frontal activity and ventral striatal (VST) dopamine (DA) transmission. Using [(11) C]Raclopride (RAC) positron emission tomography (PET), we previously demonstrated that beer flavor (absent intoxication) elicited VST DA release in beer drinkers, inferred by RAC displacement. Here, a subset of subjects from this previous RAC-PET study underwent a similar paradigm during functional magnetic resonance imaging (fMRI) to test how orbitofrontal cortex (OFC) and VST blood oxygenation level-dependent (BOLD) responses to beer flavor are related to VST DA release and motivation to drink. METHODS: Male beer drinkers (n = 28, age = 24 +/- 2, drinks/wk = 16 +/- 10) from our previous PET study participated in a similar fMRI paradigm wherein subjects tasted their most frequently consumed brand of beer and Gatorade((R)) (appetitive control). We tested for correlations between BOLD activation in fMRI and VST DA responses in PET, and drinking-related variables. RESULTS: Compared to Gatorade, beer flavor increased wanting and desire to drink, and induced BOLD responses in bilateral OFC and right VST. Wanting and desire to drink correlated with both right VST and medial OFC BOLD activation to beer flavor. Like the BOLD findings, beer flavor (relative to Gatorade) again induced right VST DA release in this fMRI subject subset, but there was no correlation between DA release and the magnitude of BOLD responses in frontal regions of interest. CONCLUSIONS: Both imaging modalities showed a right-lateralized VST response (BOLD and DA release) to a drug-paired conditioned stimulus, whereas fMRI BOLD responses in the VST and medial OFC also reflected wanting and desire to drink. The data suggest the possibility that responses to drug-paired cues may be rightward biased in the VST (at least in right-handed males) and that VST and OFC responses in this gustatory paradigm reflect stimulus wanting.

Dopamine receptor pharmacology.[Pubmed:7940991]

Trends Pharmacol Sci. 1994 Jul;15(7):264-70.

Dopamine receptors are the primary targets in the treatment of schizophrenia, Parkinson's disease, and Huntington's chorea, and are discussed in this review by Philip Seeman and Hubert Van Tol. Improved therapy may be obtained by drugs that selectively target a particular subtype of dopamine receptor. Most antipsychotic drugs block D2 receptors in direct correlation to clinical potency, except clozapine, which prefers D4 receptors. D1 and D2 receptors can enhance each other's actions, possibly through subunits of the G proteins. In schizophrenia, the D2 and D3 receptor density is elevated by 10%, while the D4 receptor density is elevated by 600%. Therefore, D4 receptors may be a target for future antipsychotic drugs. While antipsychotics originally helped to discover dopamine receptors, the five cloned dopamine receptors are now facilitating the discovery of selective antipsychotic and antiparkinson drugs.

The selective dopamine D2 receptor antagonist raclopride discriminates between dopamine-mediated motor functions.[Pubmed:2947255]

Psychopharmacology (Berl). 1986;90(3):287-94.

The actions on central dopamine (DA) mechanisms of Raclopride, a new substituted benzamide, were studied by means of behavioural and biochemical methods in the rat. Raclopride blocked the in vitro binding of the dopamine D2 antagonist 3H-spiperone (IC50 = 32 nM), but not of the unselective D1 antagonist 3H-flupenthixol (IC50 greater than 100,000 nM) in rat striatum, and failed to inhibit striatal DA-sensitive adenylate cyclase in vitro (IC50 greater than 100,000 nM). Raclopride caused a dose-dependent increase in the DA metabolites HVA and DOPAC in the striatum and olfactory tubercle. Behavioural studies showed that Raclopride discriminates between the motor behaviours induced by the DA agonist apomorphine. Thus, unlike haloperidol, Raclopride blocked apomorphine-induced hyperactivity at considerably lower doses than those inhibiting oral stereotypies. Moreover, Raclopride showed a high separation between the doses for blockade of apomorphine-induced hyperactivity and those inducing catalepsy in rats. Raclopride caused a dose-dependent blockade of the specific binding of 3H-spiperone and 3H-N-n-propylnorapomorphine (3H-NPA) in vivo at doses similar to those blocking the behavioural effects of apomorphine. The maximal blockade of 3H-spiperone binding in vivo was lower for Raclopride than for haloperidol. Raclopride caused a greater inhibition of 3H-NPA than of 3H-spiperone in vivo binding in the striatum. It is suggested that the ability of Raclopride to discriminate between different DA-mediated functions may be attributed to a preferential blockade of a subclass of functionally coupled dopamine D2 receptors in striatal as well as in extrastriatal brain regions in the rat.

Raclopride is a dopamine D2/D3 receptor antagonist, which binds to D2 and D3 receptors with dissociation constants (Kis) of 1.8 nM and 3.5 nM, respectively, but has a very low affinity for D1 and D4 receptors with Kis of 18000 nM and 2400 nM, respectively.

Raclopride,84225-95-6,Natural Products,Dopamine Receptor, buy Raclopride , Raclopride supplier , purchase Raclopride , Raclopride cost , Raclopride manufacturer , order Raclopride , high purity Raclopride