Rapid communicationAutoradiographic evidence for the occlusion of rat brain dopamine D3 receptors in vivo
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Cited by (50)
Positron emission tomography imaging of dopamine D<inf>2</inf> receptors using a highly selective radiolabeled D<inf>2</inf> receptor partial agonist
2013, NeuroImageCitation Excerpt :Because of the high affinity of dopamine for D3 receptors, it was necessary to deplete the synapse dopamine of [18F]LS-3-134 in anesthetized rhesus monkeys in order to image the D3 receptor. These data are consistent with previous reports demonstrating that there is a high in vivo occupancy of D3 receptors by endogenous dopamine (Schotte et al., 1992, 1996). That study also demonstrated that [18F]LS-3-134 had high binding in the thalamus which is believed to be a brain region having a high density of D3 receptors (Rabiner et al., 2009; Sun et al., 2012).
Cariprazine (RGH-188), a potent D<inf>3</inf>/D<inf>2</inf> dopamine receptor partial agonist, binds to dopamine D<inf>3</inf> receptors in vivo and shows antipsychotic-like and procognitive effects in rodents
2011, Neurochemistry InternationalCitation Excerpt :Our synthesis and screening efforts identified cariprazine (formerly RGH-188, Fig. 1), a compound with D3/D2 partial agonism and preference to the D3 receptor (Kiss et al., 2010). Based on theoretical considerations as well as experimental findings (Richtand et al., 2001; Schotte et al., 1992), the D3 receptor is assumed to be tonically occupied by endogenous DA. Therefore, cariprazine, as a D3 receptor partial agonist, presumably exerts antagonist-like actions in vivo by inhibiting the binding of the full agonist dopamine, and it behaves as a D2 receptor antagonist in the basal ganglia of schizophrenic patients where dopaminergic transmission is increased (Abi-Dargham et al., 2000).
Effects of antipsychotics on D3 receptors: A clinical PET study in first episode antipsychotic naive patients with schizophrenia using [ <sup>11</sup>C]-(+)-PHNO
2011, Schizophrenia ResearchCitation Excerpt :The lack of D3 blockade of D3 in vivo, as compared to what is observed in vitro (Freedman et al., 1994; van Vliet et al., 2000), has been discussed by McCormick and coworkers in detail (McCormick et al., 2010). Potential explanations include either differential endogenous dopamine occupancy at D2versus D3 (Schotte et al., 1992, 1996), or selective disruption of the high-affinity state of the receptors in vitro, but not in vivo (Sibley et al., 1983). Further, other potential differences exist between in vitro, ex vivo and in vivo conditions (e.g., disruption of ionic gradients, membrane voltage and protein kinase/phosphatase cycles, different room/body temperature, binding data analysis, etc), that could account for these differences.
A decade of progress in the discovery and development of 'atypical' antipsychotics
2010, Progress in Medicinal ChemistryCitation Excerpt :These compounds show a preference for D3 over D2 receptors and have often been termed ‘optimized D3 antagonists’ [117]. The propensity for preferential D3 antagonism is due to the fact that dopamine shows higher affinity for D3 over D2 receptors and these are likely to be fully occupied in vivo by dopamine under basal conditions [152, 153]. Hence, a compound should have a higher affinity for D3 than for D2 receptors to show in vivo activities mediated by both receptors [154].
Positron emission tomographic evaluation of the putative dopamine-D3 receptor ligand, [<sup>11</sup>C]RGH-1756 in the monkey brain
2004, Neurochemistry International