In Vivo D2 Dopamine Receptor Density in Psychotic and Nonpsychotic Patients With Bipolar Disorder

1995 ◽  
Vol 52 (6) ◽  
pp. 471 ◽  
Author(s):  
Godfrey D. Pearlson
Keyword(s):  
Bipolar Disorder ◽  
Dopamine Receptor ◽  
Receptor Density ◽  
D2 Dopamine Receptor

scholarly journals Quantification of Neuroreceptors in the Living Human Brain: III. D2-Like Dopamine Receptors: Theory, Validation, and Changes during Normal Aging

1997 ◽  
Vol 17 (3) ◽  
pp. 316-330 ◽  
Author(s):  
Dean F. Wong ◽  
David Young ◽  
P. David Wilson ◽  
Carolyn Cidis Meltzer ◽  
Albert Gjedde
Keyword(s):  
Human Brain ◽  
Dopamine Receptor ◽  
Normal Aging ◽  
Receptor Density ◽  
Least Squares Regression ◽  
Noise Levels ◽  
Normal Humans ◽  
Statistical Noise

Dopamine receptor density is believed to decline in normal aging. To test this hypothesis, we measured the density of dopamine D2-like receptors in vivo in the neostriatum of normal living humans by using the graphical method. This method determines the D2-like dopamine receptor density in the human brain with an occupying ligand (unlabeled haloperidol) and a radioligand (labeled 3- N-methylspiperone). The method was examined critically, and the assumptions underlying the method were shown to be valid. The validation included comparison of the representation of tracer metabolism by high-pressure liquid chromatography and model assays, calculation of the lumped constant Dw from the value of its components, and comparable tracer partition coefficients in vitro and in vivo. In error analysis, the method consistently performed as well as the direct least-squares regression at statistical noise levels appropriate for the tomograph used in these studies. The method revealed that the density of the D2-like receptors that bind haloperidol in the caudate nucleus of normal humans declined 1% per year after the age of 18 years.

scholarly journals μ-opioid/D2 dopamine receptor pharmacophore containing ligands: Synthesis and pharmacological evaluation

2020 ◽  
Vol 85 (6) ◽  
pp. 711-720
Author(s):  
Ivana Jevtic ◽  
Jelena Penjisevic ◽  
Katarina Savic-Vujovic ◽  
Dragana Srebro ◽  
Sonja Vuckovic ◽  
...  
Keyword(s):  
Dopamine Receptor ◽  
Opioid Receptor ◽  
General Structure ◽  
D2 Receptors ◽  
Antinociceptive Activity ◽  
D2 Dopamine Receptor ◽  
Pharmacological Evaluation ◽  
Pharmacological Tests

Herein, the synthesis and pharmacological evaluation of 13 novel compounds, designed as potential heterobivalent ligands for ?-opioid receptor (MOR) and dopamine D2 receptors (D2DAR), are reported. The compounds consisted of anilido piperidine and N-aryl piperazine moieties, joined by a variable-length methylene linker. The two moieties represent MOR and D2DAR pharmacophores, respectively. The synthesis encompassed four steps, securing the final products in 28?42 % overall yields. The approach has a considerable synthetic potential, providing access to various related structures. Pharmacological tests involved in vitro competitive assay for D2DAR using [3H] spiperon, as a standard radioligand, and in vivo antinociceptive tests for MOR. The measured dopamine affinities were modest to low, while antinociceptive activity was completely absent. Therefore, the compounds of the general structure prepared in this research are unlikely to be useful as opioid?dopamine receptor heterobivalent ligands.

scholarly journals Evaluation of Substituted N-Phenylpiperazine Analogs as D3 vs. D2 Dopamine Receptor Subtype Selective Ligands

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3182
Author(s):  
Boeun Lee ◽  
Michelle Taylor ◽  
Suzy A. Griffin ◽  
Tamara McInnis ◽  
Nathalie Sumien ◽  
...  
Keyword(s):  
Dopamine Receptor ◽  
Involuntary Movement ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Inhibition Assay ◽  
D2 Dopamine Receptor ◽  
Selective Ligand ◽  
6 Hydroxydopamine ◽  
Subtype Selective

N-phenylpiperazine analogs can bind selectively to the D3 versus the D2 dopamine receptor subtype despite the fact that these two D2-like dopamine receptor subtypes exhibit substantial amino acid sequence homology. The binding for a number of these receptor subtype selective compounds was found to be consistent with their ability to bind at the D3 dopamine receptor subtype in a bitopic manner. In this study, a series of the 3-thiophenephenyl and 4-thiazolylphenyl fluoride substituted N-phenylpiperazine analogs were evaluated. Compound 6a was found to bind at the human D3 receptor with nanomolar affinity with substantial D3 vs. D2 binding selectivity (approximately 500-fold). Compound 6a was also tested for activity in two in-vivo assays: (1) a hallucinogenic-dependent head twitch response inhibition assay using DBA/2J mice and (2) an L-dopa-dependent abnormal involuntary movement (AIM) inhibition assay using unilateral 6-hydroxydopamine lesioned (hemiparkinsonian) rats. Compound 6a was found to be active in both assays. This compound could lead to a better understanding of how a bitopic D3 dopamine receptor selective ligand might lead to the development of pharmacotherapeutics for the treatment of levodopa-induced dyskinesia (LID) in patients with Parkinson’s disease.

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