Disease relevance of RACLOPRIDE

• To gain insight into basal ganglia dysfunction in this form of hereditary parkinsonism, positron emission tomography (PET) with 18-fluorodopa (FDOPA) and 11C-raclopride (RAC) was performed in 5 affected family members and 5 asymptomatic relatives with proven compound heterozygous or heterozygous parkin mutations [1].
• Significantly, drugs with a prominent 5-HT(2A)-receptor blocking action could effectively restore the burst firing mode, i.e. phasic responsivity, in mesocortically projecting DA neurons, and also potentiate the CAR suppressant effect of the selective D(2)/D(3)-receptor antagonist raclopride without increasing catalepsy scores [2].
• However, the D2-like dopamine receptor antagonists haloperidol and raclopride, but not the D1-like dopamine receptor antagonist SCH23390, blocked the amphetamine-induced reduction in locomotor activity in coloboma mice, providing direct evidence that D2-like dopamine receptors mediate the effect of amphetamine in these mice [3].
• Furthermore, raclopride-induced acute dyskinesia worsened during chronic treatment [4].
• NNC 756 induced no dystonia, while marked dystonia was induced by raclopride [4].

Psychiatry related information on RACLOPRIDE

• We found that the typical antipsychotic raclopride was much less potent in inhibiting locomotor activity and eliciting catalepsy (or parkinsonism) in D2L(-/-) mice, whereas the atypical antipsychotic clozapine was equally effective in D2L(-/-) and wild-type mice [5].
• In contrast, blocking dopamine receptors with the selective D2 antagonist raclopride was found to induce opposite effects on the reaction time performance [6].
• The incidence and duration of akathisia seem to be mainly related to the plasma raclopride concentrations over time, whereas the rate of administration might be more important for the severity [7].
• Effects of D2 dopamine receptor blockade with raclopride on intracranial self-stimulation and food-reinforced operant behaviour [8].
• The selective DA D-2 antagonists, raclopride (0.03-1 mg/kg s.c.) and remoxipride (1-10 mg/kg s.c.), did not affect sleep stages [9].

High impact information on RACLOPRIDE

• Binding of raclopride to dopamine receptors in the striatum was significantly reduced during the video game compared with baseline levels of binding, consistent with increased release and binding of dopamine to its receptors [10].
• The reduction in binding of raclopride in the striatum positively correlated with the performance level during the task and was greatest in the ventral striatum [10].
• MAIN OUTCOME MEASURES: Results of positron emission tomography with raclopride C 11 to assess D(2) receptors and with fludeoxyglucose F 18 to assess brain glucose metabolism (marker of brain function) [11].
• They were examined repeatedly with positron emission tomography and the radioligand carbon 11-labeled raclopride during the following year [12].
• Using positron emission tomography and the carbon 11-labeled ligand raclopride, central D2-dopamine receptor occupancy in the putamen was determined in psychiatric patients treated with clinical doses of psychoactive drugs [13].

Chemical compound and disease context of RACLOPRIDE

• One week after a saline or STZ injection (50 mg/kg), rats were treated with amphetamine (1.78 mg/kg), raclopride (0.056 mg/kg), saline, or combinations thereof, every-other-day for 8 days with locomotor activity measured following each treatment [14].
• Reboxetine (6 mg/kg, i.p.) significantly enhanced the suppressant effect of raclopride (0.1 mg/kg, s.c.) on CAR without affecting catalepsy [15].
• Both the selective D-2 antagonist raclopride and the selective D-1 antagonist SCH 23390 inhibited normal locomotor activity and induced catalepsy [16].
• Savoxepine, clozapine, haloperidol, olanzapine, ORG 5222, raclopride, and risperidone were examined in two tests for catalepsy (grid and bar tests) in male Sprague-Dawley rats [17].
• Concomitant treatment with NNC 756 tended to reduce the D1 agonist SKF 81297-induced dyskinesia and grooming, while concomitant treatment with raclopride increased SKF 81297-induced dyskinesia and tended to decrease SKF 81297-induced grooming [4].

Biological context of RACLOPRIDE

• The antipsychotic drug raclopride, a selective D2 receptor antagonist, increased phosphorylation of DARPP-32 under basal conditions and in D2 agonist-treated slices [18].
• In blocking studies, baboons were pretreated with N-methyl-2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (CFT, 14 mg) or raclopride (14 mg) to block DAT or D2/D3 binding site, respectively [19].
• Pharmacokinetics of raclopride formulations. Influence of prolactin and tolerability in healthy male volunteers [20].
• All three compounds suppressed water consumption, but only SCH and RAC decreased drinking efficiency [21].
• Pretreatment with the centrally acting selective dopamine D2 receptor antagonist raclopride, but not the D1 antagonist SCH23390, completely prevented the rise in blood pressure [22].

Anatomical context of RACLOPRIDE

• Following unilateral fimbriaectomy, whereby at least 50% of hippocampal cholineacetyltransferase (ChAT) activity was lost, a significant ipsilateral decrease in D1/3H SCH23390 binding was observed in the molecular layer of the dentate gyrus while hippocampal D2/3H raclopride binding was unaffected [23].
• Pretreatment with raclopride blocked the increments, but raclopride alone did not alter baseline values of k*. In independent experiments, D-amphetamine 0.5 mg/kg i.p. increased k* significantly in only seven regions, including the nucleus accumbens and layer IV neocortical regions [24].
• In contrast to raclopride alone, combined L-dopa/raclopride also produced a much larger increase in DA output in the prefrontal cortex than in the nucleus accumbens [25].
• Performance on different cognitive tests, especially in timed tasks, was highly correlated with raclopride C11 binding in caudate nucleus and ventral striatum [26].
• This study reports that chronic blockade (21 days) of either dopamine D1 receptors by SCH-23390 or dopamine D2 receptors by raclopride does not affect the concentrations of DARPP-32 in specific rat brain regions (striatum, thalamus, hippocampus, frontal cerebral cortical pole) [27].

Associations of RACLOPRIDE with other chemical compounds

• Acute administration of the dopamine receptor antagonist pimozide or the specific dopamine D2 receptor antagonist raclopride had no effect in nonstressed animals and in vehicle-treated stressed animals, but both drugs selectively reversed the improvement of performance in imipramine-treated stressed animals [28].
• D2 blockade with haloperidol or raclopride increased, whereas D2 stimulation with LY-171555 (D2 agonist) decreased, striatal and accumbens proenkephalin mRNA abundance [29].
• Comparison of the effects of remoxipride and raclopride on nigrostriatal and mesolimbic dopaminergic neuronal activity and on the secretion of prolactin and alpha-melanocyte-stimulating hormone [30].
• The 5-HT1C/2 antagonist, ritanserin, the 5-HT3 antagonist, ondansetron, the dopamine D2 receptor antagonist, raclopride, and the alpha 1-adrenoceptor antagonist, prazosin, were also ineffective in modifying the antinociception evoked by 5-HT1A agonists and partial agonists in the hot-plate test [31].
• Administration of raclopride (0.1 mg/kg, s.c.) to rats pretreated with reboxetine (6 mg/kg, i.p.) resulted in a greatly enhanced effect on DA output in the mPFC but not in the nucleus accumbens when compared with raclopride alone [15].

Gene context of RACLOPRIDE

• There was no difference in phosphorylated TH levels or TH catalytic activity between wild-type and alpha-synuclein knockout mice under basal conditions or following raclopride-induced acceleration of NSDA activity [32].
• Furthermore, to determine whether NMDA receptor subtype dependence of haloperidol-induced c-Fos expression is unique to the binding profile of haloperidol or whether it is a property of D2 receptor antagonism, the selective D2/D3 dopamine receptor antagonist, raclopride, was also used [33].
• The effect of neurotensin was abolished by tetrodotoxin (TTX) or MK801 plus CNQX, but not by SCH23390 or raclopride [34].
• DA-D2 and glutamate receptors of NMDA subtypes also participate, albeit to a lesser extent, to THC-induced ERK activation in the striatum, as shown after injection of selective antagonists (raclopride and MK801, respectively) [35].
• We used dopamine transporter (DAT) (-/-) mice to examine the behavioral consequences of a chronically hyperdopaminergic state, challenging them with the preferential dopamine D2 receptor antagonist raclopride and D1 receptor antagonist SCH23390 [36].

Analytical, diagnostic and therapeutic context of RACLOPRIDE

• Local perfusion of the D(2-3) receptor antagonist raclopride produced an increase in the extracellular levels of dopamine, which was partially, but significantly, counteracted by coperfusion with dihydro-beta-erythroidine [37].
• In contrast, the selective D2 receptor antagonist raclopride caused a greater activation of the subcortical than cortical DA projections, as assessed by microdialysis experiments in vivo from our laboratory [38].
• Raclopride (0.25 and 0.5 mg/kg SC) and SCH23390 (0.01 and 0.02 mg/kg SC) blocked the amphetamine-induced hyperlocomotion in the lesioned and control groups [39].
• In this exploratory, double-blind study, the relationship between plasma prolactin concentration and central D2 receptor occupancy was examined in 13 schizophrenic patients treated with the experimental antipsychotic drug raclopride (2, 6, or 12 mg daily) [40].
• The D2 receptor blocker, raclopride, alone (1-3 mg/kg i.v.) produced changes of the activity of the EEG, mostly, short periods of slow waves and slight increases of total power [41].

References