ChemInform Abstract: Synthesis and Pharmacological Properties of Novel 8-Substituted Imidazobenzodiazepines: High-Affinity, Selective Probes for α5- Containing GABAA Receptors.

ChemInform ◽  
2010 ◽  
Vol 27 (33) ◽  
pp. no-no
Author(s):  
R. LIU ◽  
R. J. HU ◽  
P. ZHANG ◽  
P. SKOLNICK ◽  
J. M. COOK
Keyword(s):  
Gabaa Receptors ◽  
Pharmacological Properties ◽  
High Affinity

GABAA receptors: Various stoichiometrics of subunit arrangement in α1β3 and α1β3ε receptors

2018 ◽  
Vol 24 (17) ◽  
pp. 1839-1844 ◽  
Author(s):  
Ahmad Tarmizi Che Has ◽  
Mary Chebib
Keyword(s):  
Central Nervous System ◽  
Gabaa Receptors ◽  
Binding Sites ◽  
New Drugs ◽  
Pharmacological Properties ◽  
Receptor Complex ◽  
The Third ◽  
Γ Subunit ◽  
Subunit Stoichiometry ◽  
The Central Nervous System

GABAA receptors are members of the Cys-loop family of ligand-gated ion channels which mediate most inhibitory neurotransmission in the central nervous system. These receptors are pentameric assemblies of individual subunits, including α1-6, β1-3, γ1-3, δ, ε, π, θ and ρ1-3. The majority of receptors are comprised of α, β and γ or δ subunits. Depending on the subunit composition, the receptors are located in either the synapses or extrasynaptic regions. The most abundant receptors are α1βγ2 receptors, which are activated and modulated by a variety of pharmacologically and clinically unrelated agents such as benzodiazepines, barbiturates, anaesthetics and neurosteroids, all of which bind at distinct binding sites located within the receptor complex. However, compared to αβγ, the binary αβ receptors lack a benzodiazepine α-γ2 interface. In pentameric αβ receptors, the third subunit is replaced with either an α1 or a β3 subunit leading to two distinct receptors that differ in subunit stoichiometry, 2α:3β or 3α:2β. The consequence of this is that 3α:2β receptors contain an α-α interface whereas 2α:3β receptors contain a β-β interface. Apart from the replacement of γ by α1 or β3 in binary receptors, the incorporation of ε subunit into GABAA receptors might be more complicated. As the ε subunit is not only capable of substituting the γ subunit, but also replacing the α/β subunits, receptors with altered stoichiometry and different pharmacological properties are produced. The different subunit arrangement of the receptors potentially constructs novel binding sites which may become new targets of the current or new drugs.

scholarly journals Tricyclic Pyrazole-Based Compounds as Useful Scaffolds for Cannabinoid CB1/CB2 Receptor Interaction

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2126
Author(s):  
Battistina Asproni ◽  
Gabriele Murineddu ◽  
Paola Corona ◽  
Gérard A. Pinna
Keyword(s):  
Neuropathic Pain ◽  
Cannabinoid Receptor ◽  
Receptor Interaction ◽  
Pharmacological Properties ◽  
Cb2 Receptor ◽  
Antiemetic Effect ◽  
High Affinity ◽  
Cb1 Antagonist ◽  
Cb2 Receptors ◽  
Sar Study

Cannabinoids comprise different classes of compounds, which aroused interest in recent years because of their several pharmacological properties. Such properties include analgesic activity, bodyweight reduction, the antiemetic effect, the reduction of intraocular pressure and many others, which appear correlated to the affinity of cannabinoids towards CB1 and/or CB2 receptors. Within the search aiming to identify novel chemical scaffolds for cannabinoid receptor interaction, the CB1 antagonist/inverse agonist pyrazole-based derivative rimonabant has been modified, giving rise to several tricyclic pyrazole-based compounds, most of which endowed of high affinity and selectivity for CB1 or CB2 receptors. The aim of this review is to present the synthesis and summarize the SAR study of such tricyclic pyrazole-based compounds, evidencing, for some derivatives, their potential in the treatment of neuropathic pain, obesity or in the management of glaucoma.

scholarly journals Novel Three-Finger Neurotoxins from Naja melanoleuca Cobra Venom Interact with GABAA and Nicotinic Acetylcholine Receptors

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 164
Author(s):  
Lina Son ◽  
Elena Kryukova ◽  
Rustam Ziganshin ◽  
Tatyana Andreeva ◽  
Denis Kudryavtsev ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Gabaa Receptors ◽  
Binding Sites ◽  
Acetylcholine Receptors ◽  
Nicotinic Acetylcholine ◽  
High Affinity ◽  
Central Loop ◽  
Acetylcholine Binding Proteins ◽  
Α7 Nachrs

Cobra venoms contain three-finger toxins (TFT) including α-neurotoxins efficiently binding nicotinic acetylcholine receptors (nAChRs). As shown recently, several TFTs block GABAA receptors (GABAARs) with different efficacy, an important role of the TFTs central loop in binding to these receptors being demonstrated. We supposed that the positive charge (Arg36) in this loop of α-cobratoxin may explain its high affinity to GABAAR and here studied α-neurotoxins from African cobra N. melanoleuca venom for their ability to interact with GABAARs and nAChRs. Three α-neurotoxins, close homologues of the known N. melanoleuca long neurotoxins 1 and 2, were isolated and sequenced. Their analysis on Torpedocalifornica and α7 nAChRs, as well as on acetylcholine binding proteins and on several subtypes of GABAARs, showed that all toxins interacted with the GABAAR much weaker than with the nAChR: one neurotoxin was almost as active as α-cobratoxin, while others manifested lower activity. The earlier hypothesis about the essential role of Arg36 as the determinant of high affinity to GABAAR was not confirmed, but the results obtained suggest that the toxin loop III may contribute to the efficient interaction of some long-chain neurotoxins with GABAAR. One of isolated toxins manifested different affinity to two binding sites on Torpedo nAChR.

High-Affinity, Selective σ Ligands of the 1,2,3,4-Tetrahydro-1,4′-silaspiro[naphthalene-1,4′-piperidine] Type: Syntheses, Structures, and Pharmacological Properties

ChemMedChem ◽  
2011 ◽  
Vol 7 (3) ◽  
pp. 523-532 ◽  
Author(s):  
Reinhold Tacke ◽  
Rüdiger Bertermann ◽  
Christian Burschka ◽  
Steffen Dörrich ◽  
Markus Fischer ◽  
...  
Keyword(s):  
Pharmacological Properties ◽  
High Affinity

scholarly journals Tonic for what ails us? high-affinity GABAA receptors and alcohol

Alcohol ◽  
2007 ◽  
Vol 41 (3) ◽  
pp. 139-143 ◽  
Author(s):  
David M. Lovinger ◽  
Gregg E. Homanics
Keyword(s):  
Gabaa Receptors ◽  
High Affinity

Pharmacological Properties of GABAA Receptors Containing γ1 Subunits

2005 ◽  
Vol 69 (2) ◽  
pp. 640-649 ◽  
Author(s):  
S. Khom ◽  
I. Baburin ◽  
E. N. Timin ◽  
A. Hohaus ◽  
W. Sieghart ◽  
...  
Keyword(s):  
Gabaa Receptors ◽  
Pharmacological Properties

Regulation of high-affinity GABAA receptors in the dorsal hippocampus by estradiol and progesterone

1989 ◽  
Vol 487 (1) ◽  
pp. 178-183 ◽  
Author(s):  
M. Schumacher ◽  
H. Coirini ◽  
B.S. McEwen
Keyword(s):  
Gabaa Receptors ◽  
Dorsal Hippocampus ◽  
High Affinity

Pharmacological properties of fetal rat hippocampal GABAA receptors

1995 ◽  
Vol 85 (2) ◽  
pp. 280-282 ◽  
Author(s):  
Alexander Y. Valeyev ◽  
Veronica S. Dunlap ◽  
Jeffery L. Barker
Keyword(s):  
Gabaa Receptors ◽  
Pharmacological Properties ◽  
Fetal Rat
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