scholarly journals Design, Synthesis, and Evaluation of Functionalized 5-(4-arylpiperazin-1-yl)-N-Quinolinyl-pentanamides as Selective Dopamine D3 Receptor Ligands

2021 ◽  
Author(s):  
Benjamin E Blass ◽  
Peng-Jen Chen ◽  
Michelle Taylor ◽  
Suzy A Griffin ◽  
John C Gordon ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Receptor Ligands ◽  
Design Synthesis ◽  
Amino Acid Homology ◽  
Affinity Ligands ◽  
The Central Nervous System ◽  
Dopamine D3 ◽  
Physiological Impact ◽  
G Protein Coupled ◽  
Selective Dopamine

Abstract Dopamine (1) plays a key role in normal physiological pathways in both the central nervous system and the periphery. The physiological impact of this neurotransmitter is mediated through its interaction with family of G-protein-coupled receptors (GPCRs). These receptors are designated as D1, D2, D3, D4, and D5 and divided into two sub-families, the D1-like sub-family (D1 and D5) and D2-like sub-family (D2, D3 and D4) based on pharmacological properties, amino acid homology, and genetic organization. Aberrant D3 activity has been linked to multiple diseases and conditions such as depression, schizophrenia, substance use disorder, inflammatory diseases, and Parkinson’s disease (PD). As part of our on-going program focused on the identification of novel D3 ligands, we have identified a novel series of 5-(4-arylpiperazin-1-yl)-N-quinolinyl-pentanamides that are high affinity ligands for this receptor.

Design, Synthesis, and Evaluation of Indolebutylamines as a Novel Class of Selective Dopamine D3 Receptor Ligands

2013 ◽  
Vol 82 (3) ◽  
pp. 326-335 ◽  
Author(s):  
Peng Du ◽  
Lili Xu ◽  
Jiye Huang ◽  
Kunqian Yu ◽  
Rui Zhao ◽  
...  
Keyword(s):  
Dopamine D3 Receptor ◽  
D3 Receptor ◽  
Receptor Ligands ◽  
Design Synthesis ◽  
Dopamine D3 ◽  
Selective Dopamine

Design, synthesis, and evaluation of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamides as selective dopamine D3 receptor ligands

2019 ◽  
Vol 29 (18) ◽  
pp. 2690-2694 ◽  
Author(s):  
Peng-Jen Chen ◽  
Michelle Taylor ◽  
Suzy A. Griffin ◽  
Armaghan Amani ◽  
Hamed Hayatshahi ◽  
...  
Keyword(s):  
Dopamine D3 Receptor ◽  
D3 Receptor ◽  
Receptor Ligands ◽  
Design Synthesis ◽  
Dopamine D3 ◽  
Selective Dopamine

scholarly journals Design, Synthesis, And Evaluation of Functionalized Diamino-butylbenzamides As Selective Dopamine D3 Receptor Ligands

2021 ◽  
Author(s):  
Benjamin E Blass ◽  
Peng-Jen Chen ◽  
Michelle Taylor ◽  
Suzy A Griffin ◽  
John C Gordon ◽  
...  
Keyword(s):  
High Selectivity ◽  
Recreational Drugs ◽  
Dopamine D3 Receptor ◽  
D3 Receptor ◽  
Receptor Ligands ◽  
Potential Therapeutic Target ◽  
Design Synthesis ◽  
Medical Need ◽  
Dopamine D3 ◽  
Selective Dopamine

Abstract Substance use disorder remains a major, unmet medical need. Cocaine is one of the most commonly abused recreational drugs and in 2018, there were over 5.5 million current cocaine users. There are no approved therapies for the treatment of cocaine use disorder, but the D3 dopamine receptor has been identified as a potential therapeutic target. We have identified a series of functionalized diamino-butylbenzamides that are potent D3 binders with moderate to high selectivity for D3 over D2.

Clinical applications of single photon emission tomography in neuromedicine

2000 ◽  
Vol 39 (08) ◽  
pp. 218-231 ◽  
Author(s):  
F. Grünwald ◽  
T. Kuwert ◽  
K. Tatsch ◽  
O. Sabri ◽  
O. Benkert ◽  
...  
Keyword(s):  
Single Photon ◽  
Inflammatory Diseases ◽  
Photon Emission ◽  
Clinical Applications ◽  
Emission Tomography ◽  
Receptor Ligands ◽  
Single Photon Emission ◽  
The Central Nervous System ◽  
Dementing Disorders ◽  
Photon Emission Tomography

SummaryThis article gives in his second part a critical review of the clinical applications of SPECT with perfusion markers and receptor ligands in dementing disorders and psychosis. In addition this review discusses clinical applications of SPECT investigations with perfusion markers in inflammatory diseases of the central nervous system and in brain trauma.

scholarly journals Bivalent ligands promote endosomal trafficking of the dopamine D3 receptor-neurotensin receptor 1 heterodimer

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Julian Budzinski ◽  
Simone Maschauer ◽  
Hiroyuki Kobayashi ◽  
Pierre Couvineau ◽  
Hannah Vogt ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Receptor Interaction ◽  
Endosomal Trafficking ◽  
Receptor Ligands ◽  
Bivalent Ligands ◽  
Neurotensin Receptor ◽  
Neuropsychiatric Diseases ◽  
Dopamine D3 ◽  
Neurotensin Receptor 1 ◽  
G Protein Coupled

AbstractBivalent ligands are composed of two pharmacophores connected by a spacer of variable size. These ligands are able to simultaneously recognize two binding sites, for example in a G protein-coupled receptor heterodimer, resulting in enhanced binding affinity. Taking advantage of previously described heterobivalent dopamine-neurotensin receptor ligands, we demonstrate specific interactions between dopamine D3 (D3R) and neurotensin receptor 1 (NTSR1), two receptors with expression in overlapping brain areas that are associated with neuropsychiatric diseases and addiction. Bivalent ligand binding to D3R-NTSR1 dimers results in picomolar binding affinity and high selectivity compared to the binding to monomeric receptors. Specificity of the ligands for the D3R-NTSR1 receptor pair over D2R-NTSR1 dimers can be achieved by a careful choice of the linker length. Bivalent ligands enhance and stabilize the receptor-receptor interaction leading to NTSR1-controlled internalization of D3R into endosomes via recruitment of β-arrestin, highlighting a potential mechanism for dimer-specific receptor trafficking and signalling.

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