Selective Ligands for Benzodiazepine Receptors: Recent Developments

1990 ◽  
pp. 259-293 ◽  
Author(s):  
David Nutt
Keyword(s):  
Benzodiazepine Receptors ◽  
Selective Ligands ◽  
Recent Developments

Synthesis of substituted [123I]imidazo[1,2-α]pyridines as potential probes for the study of the peripheral benzodiazepine receptors using SPECT

2000 ◽  
Vol 88 (3-4) ◽  
Author(s):  
Andrew Katsifis ◽  
F. Mattner ◽  
B. Dikic ◽  
V. Papazian
Keyword(s):  
Benzodiazepine Receptors ◽  
High Affinity ◽  
Peripheral Benzodiazepine Receptors ◽  
Selective Ligands

The imidazo[1,2-α]pyridines [N,N´-dimethyl-6-chloro-(4´zf-iodophenyl)imidazo[1,2-α]pyridine-3-acetamide 1, [N,N´l-6-chloro-(4´-iodophenyl)imidazo[1,2-α]pyridine-3-acetamide 2, and [N-methyl-6-chloro-(4´-iodophenyl)imidazo[1,2-α]pyridine-3-acetamide 3, are high affinity and selective ligands for the Peripheral Benzodiazepine Receptors (PBR). The [

scholarly journals Current Developments on the Role of α1-Adrenergic Receptors in Cognition, Cardioprotection, and Metabolism

2021 ◽  
Vol 9 ◽  
Author(s):  
Dianne M. Perez
Keyword(s):  
Adrenergic Receptors ◽  
Smooth Muscle Contraction ◽  
The Body ◽  
Whole Body ◽  
Selective Ligands ◽  
Recent Developments ◽  
Vascular Smooth Muscle Contraction ◽  
G Protein Coupled ◽  
Similar Affinity

The α1-adrenergic receptors (ARs) are G-protein coupled receptors that bind the endogenous catecholamines, norepinephrine, and epinephrine. They play a key role in the regulation of the sympathetic nervous system along with β and α2-AR family members. While all of the adrenergic receptors bind with similar affinity to the catecholamines, they can regulate different physiologies and pathophysiologies in the body because they couple to different G-proteins and signal transduction pathways, commonly in opposition to one another. While α1-AR subtypes (α1A, α1B, α1C) have long been known to be primary regulators of vascular smooth muscle contraction, blood pressure, and cardiac hypertrophy, their role in neurotransmission, improving cognition, protecting the heart during ischemia and failure, and regulating whole body and organ metabolism are not well known and are more recent developments. These advancements have been made possible through the development of transgenic and knockout mouse models and more selective ligands to advance their research. Here, we will review the recent literature to provide new insights into these physiological functions and possible use as a therapeutic target.

Recent Developments in Bioassay Using Selective Ligands and Selective In Vitro Preparations

1986 ◽  
Author(s):  
Hans W. Kosterlitz ◽  
◽  
Alistair D. Corbett ◽  
Maureen G. C. Gillan ◽  
Alexander T. McKnight ◽  
...  
Keyword(s):  
Selective Ligands ◽  
Recent Developments

Recent Developments on Future Antidepressant-related Serotonin Receptors

2018 ◽  
Vol 24 (22) ◽  
pp. 2541-2548 ◽  
Author(s):  
Meysam Amidfar ◽  
Yong-Ku Kim
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Rapid Onset ◽  
Mechanisms Of Action ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Onset Of Action ◽  
Antidepressant Effects ◽  
Selective Ligands ◽  
Recent Developments ◽  
Synaptic Neurotransmission

Conventional serotonin-enhancing antidepressants including selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) have shown effectiveness in the treatment of major depression, but their significant limitations such as slowness of action have led to intensive research efforts to develop new antidepressants. Increased synaptic neurotransmission of serotonin (5-hdroxytryptamine; 5-HT) through orchestration of stimulation and blockade of various subtypes of 5-HT receptors is involved in the mechanisms of action of SSRIs. Agonists at the 5-HT1A, 5-HT1B, 5-HT2C, 5-HT4, and 5-HT6 receptors and antagonists at the 5-HT1A, 5-HT2A, 5-HT2C, 5-HT3, 5- HT6, and 5-HT7 receptors have shown antidepressant properties in clinical and preclinical studies. However, paradoxical antidepressant-like effects of both agonists and antagonists at particular 5-HT receptors suggest the need to consider the neurochemical mechanisms of each 5-HT receptor subtype. Therefore, better knowledge of the involvement of individual 5-HT receptors in the mechanisms of action of currently used antidepressants as well as antidepressant effects of selective ligands of 5- HT receptor subtypes will provide opportunities for the development of future antidepressants with more rapid onset of action, fewer side effects, and better efficacy than SSRIs.

scholarly journals A Review of the Updated Pharmacophore for the Alpha 5 GABA(A) Benzodiazepine Receptor Model

2015 ◽  
Vol 2015 ◽  
pp. 1-54 ◽  
Author(s):  
Terry Clayton ◽  
Michael M. Poe ◽  
Sundari Rallapalli ◽  
Poonam Biawat ◽  
Miroslav M. Savić ◽  
...  
Keyword(s):  
Structural Characteristics ◽  
Benzodiazepine Receptor ◽  
Binding Pocket ◽  
Positive Allosteric Modulator ◽  
Gaba A ◽  
Behavioral Studies ◽  
Selective Ligands ◽  
Recent Developments ◽  
Molecular Modeling Studies ◽  
Subtype Selective

An updated model of the GABA(A) benzodiazepine receptor pharmacophore of the α5-BzR/GABA(A) subtype has been constructed prompted by the synthesis of subtype selective ligands in light of the recent developments in both ligand synthesis, behavioral studies, and molecular modeling studies of the binding site itself. A number of BzR/GABA(A) α5 subtype selective compounds were synthesized, notably α5-subtype selective inverse agonist PWZ-029 (1) which is active in enhancing cognition in both rodents and primates. In addition, a chiral positive allosteric modulator (PAM), SH-053-2′F-R-CH3 (2), has been shown to reverse the deleterious effects in the MAM-model of schizophrenia as well as alleviate constriction in airway smooth muscle. Presented here is an updated model of the pharmacophore for α5β2γ2 Bz/GABA(A) receptors, including a rendering of PWZ-029 docked within the α5-binding pocket showing specific interactions of the molecule with the receptor. Differences in the included volume as compared to α1β2γ2, α2β2γ2, and α3β2γ2 will be illustrated for clarity. These new models enhance the ability to understand structural characteristics of ligands which act as agonists, antagonists, or inverse agonists at the Bz BS of GABA(A) receptors.

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