Negative allosteric modulators of NMDA receptors with GluN2B subunit: Alanine‐derived benzoxazolone bioisosteres of 2‐methyl‐3‐benzazepine‐1,7‐diols
Sign Up to like & getrecommendations! Published in 2022 at "Archiv der Pharmazie"
DOI: 10.1002/ardp.202200177
Abstract: Inspired by besonprodil, the phenol of potent negative allosteric modulators of GluN2B‐N‐methyl‐d‐aspartate (NMDA) receptors was replaced by a benzoxazolone system. To increase the similarity to the lead compounds, an additional methyl moiety was installed in… read more here.
Keywords: nmda receptors; allosteric modulators; moiety; benzoxazolone ... See more keywords
Opportunities and Challenges in the Discovery of Allosteric Modulators of GPCRs.
Sign Up to like & getrecommendations! Published in 2018 at "Methods in molecular biology"
DOI: 10.1007/978-1-4939-7465-8_13
Abstract: From the pharmacological point of view, allosteric modulators may present numerous advantages over orthosteric ligands. Growing availability of novel tools and experimental data provides a tempting opportunity to apply computational methods to improve known modulators… read more here.
Keywords: modulators gpcrs; challenges discovery; allosteric modulators; opportunities challenges ... See more keywords
The NMDA receptor intracellular C‐terminal domains reciprocally interact with allosteric modulators
Sign Up to like & getrecommendations! Published in 2019 at "Biochemical Pharmacology"
DOI: 10.1016/j.bcp.2018.11.018
Abstract: &NA; N‐methyl‐D‐aspartate receptors (NMDARs) have multiple prominent roles in CNS function but their excessive or insufficient activity contributes to neuropathological/psychiatric disorders. Consequently, a variety of positive and negative allosteric modulators (PAMs and NAMs, respectively) have… read more here.
Keywords: terminal domains; allosteric modulators; intracellular terminal; pam activity ... See more keywords
Development of 1,3-thiazole analogues of imidazopyridines as potent positive allosteric modulators of GABAA receptors.
Sign Up to like & getrecommendations! Published in 2019 at "Bioorganic chemistry"
DOI: 10.1016/j.bioorg.2019.103334
Abstract: Structure-activity relationship studies were conducted in the search for 1,3-thiazole isosteric analogs of imidazopyridine drugs (Zolpidem, Alpidem). Three series of novel γ-aminobutyric acid receptor (GABAAR) ligands belonging to imidazo[2,1-b]thiazoles, imidazo[2,1-b][1,3,4]thiadiazoles, and benzo[d]imidazo[2,1-b]thiazoles were synthesized and… read more here.
Keywords: allosteric modulators; development thiazole; development; imidazo thiazoles ... See more keywords
Virtual Screening in Search of Allosteric Modulators of Nav1.1 Channels
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DOI: 10.1016/j.bpj.2016.11.1325
Abstract: Voltage-gated Na+ (Nav) channels provide the basis for neuronal excitability in the brain. Of the nine Nav channel isoforms (Nav1.1-Nav1.9), Nav1.1 exhibits cell-specific distribution in fast-spiking parvalbumin (PV) interneurons in the cortical circuit. Reduced function… read more here.
Keywords: virtual screening; search allosteric; fgf14 nav1; screening search ... See more keywords
Agonists and allosteric modulators promote signaling from different metabotropic glutamate receptor 5 conformations
Sign Up to like & getrecommendations! Published in 2021 at "Cell Reports"
DOI: 10.1016/j.celrep.2021.109648
Abstract: Summary Metabotropic glutamate receptors (mGluRs) are dimeric G-protein-coupled receptors activated by the main excitatory neurotransmitter, L-glutamate. mGluR activation by agonists binding in the venus flytrap domain is regulated by positive (PAM) or negative (NAM) allosteric… read more here.
Keywords: metabotropic glutamate; allosteric modulators; agonists allosteric; receptor ... See more keywords
Muscarinic receptor M4 positive allosteric modulators attenuate central effects of cocaine.
Sign Up to like & getrecommendations! Published in 2017 at "Drug and alcohol dependence"
DOI: 10.1016/j.drugalcdep.2017.03.014
Abstract: BACKGROUND Cocaine addiction is a chronic brain disease affecting neurotransmission. Muscarinic cholinergic receptors modulate dopaminergic signaling in the reward system, and muscarinic receptor stimulation can block direct reinforcing effects of cocaine. Here, we tested the… read more here.
Keywords: allosteric modulators; muscarinic receptor; cocaine; effects cocaine ... See more keywords
Subtle modifications to a thieno[2,3-d]pyrimidine scaffold yield negative allosteric modulators and agonists of the dopamine D2 receptor.
Sign Up to like & getrecommendations! Published in 2019 at "European journal of medicinal chemistry"
DOI: 10.1016/j.ejmech.2019.01.061
Abstract: We recently described a structurally novel series of negative allosteric modulators (NAMs) of the dopamine D2 receptor (D2R) based on thieno[2,3-d]pyrimidine 1, showing it can be structurally simplified to reveal low molecular weight, fragment-like NAMs… read more here.
Keywords: allosteric modulators; thieno pyrimidine; negative allosteric; dopamine receptor ... See more keywords
Vasodilatory effects of a variety of positive allosteric modulators of GABAA receptors on rat thoracic aorta.
Sign Up to like & getrecommendations! Published in 2021 at "European journal of pharmacology"
DOI: 10.1016/j.ejphar.2021.174023
Abstract: Different subtypes of GABAA (gamma-aminobutyric acid A) receptors, through their specific regional and cellular localization, are involved in the manifestation of various functions, both at the central and peripheral levels. We hypothesized that various non-neuronal… read more here.
Keywords: thoracic aorta; allosteric modulators; gabaa receptors; rat thoracic ... See more keywords
Antidepressant Effects and Mechanisms of Group II mGlu Receptor-Specific Negative Allosteric Modulators
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DOI: 10.1016/j.neuron.2019.12.011
Abstract: In this issue of Neuron, Joffe et al. (2020) assess the antidepressant-relevant effects and underlying neural mechanisms of negative allosteric modulators selective for either metabotropic glutamate receptors 2 (mGlu2) or 3 (mGlu3). Negative modulation of both… read more here.
Keywords: mechanisms group; effects mechanisms; negative allosteric; allosteric modulators ... See more keywords
Identification by virtual screening and functional characterisation of novel positive and negative allosteric modulators of the α7 nicotinic acetylcholine receptor
Sign Up to like & getrecommendations! Published in 2018 at "Neuropharmacology"
DOI: 10.1016/j.neuropharm.2018.07.009
Abstract: ABSTRACT Several previous studies have demonstrated that the activity of neurotransmitters acting on ligand‐gated ion channels such as the nicotinic acetylcholine receptor (nAChR) can be altered by compounds binding to allosteric modulatory sites. In the… read more here.
Keywords: positive negative; negative allosteric; nicotinic acetylcholine; allosteric modulators ... See more keywords