Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 15 of 15 for “"positive allosteric modulators"”.
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Design, Synthesis, and Pharmacological Characterization of Serotonin (5-HT) 5-HT2C Receptor (5-HT2CR) Positive Allosteric Modulators
… and pharmacologically evaluated as 5-HT2CR positive allosteric modulators (PAMs). Several analogues potentiated intracellular calcium release by 5-HT in h5-HT2CR-CHO cells. Several compounds exhibited a favorable overall pharmacokinetic profile and modulated 5-HT2CRassociated behaviors …
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Gabab Regulation of Methamphetamine-Induced Associative Learning
… GABAB receptor agonist baclofen has revealed positive outcomes in clinical trials; however, the side effects associated with baclofen limit its clinical utility. Positive allosteric modulators (PAMs) of the GABAB receptor augment GABAB receptor signaling without the side effects of the agonist …
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Accelerated simulations and computer-aided drug design of membrane proteins
… state and retrospective docking of known positive allosteric modulators (PAMs) to GaMD simulation-derived structural ensembles of the adenosine A1 receptor (A1AR), respectively. Finally, in Chapter 5, I apply LiGaMD to understand the mechanism of ligand recognition by human Angiotensin …
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Studies in GPCR and Chromosomal Control
… of small molecule serotonin agonists and positive allosteric modulators targeting the two receptors, as well as peptide mimics of the transmembrane domains to control the receptor associations. Ewing’s Sarcoma is a malignant pediatric cancer found in bones and soft tissues. It is the …
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Novel Modulators of CD39 and CD73
… kinase inhibitors to identify novel modulators of CD39 and CD73, explore their mechanisms of action, investigate their binding sites via in-silico docking, and evaluate the ex-vivo activity of specific CD39 modulators. The malachite green assay was employed for in-vitro screening of …
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Small Molecule Allosteric Modulation of G Protein-Coupled Receptors and Applications in the Pharmacological Targeting of 5-HT2 Receptors
… target GPCRs. Predictably, small molecule allosteric modulation has emerged in recent years as a new means to control GPCR function with numerous examples nearing FDA approval. This body of work begins with a substantive review of drug discovery efforts in the development of Class A GPCR …
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Synthesis of fluorinated cannabinoid derivatives; Towards PET radiotracers for imaging the cannabinoid receptor
… leading to the development of GAT211 as CB1R-positive allosteric modulators (PAMs)5,6. In the second part of this project, we embarked on modifying structural features of GAT211. Biological assays in vitro and in vivo were used to determine if the fluorinated cannabinoid derivatives behaved as …
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Structural insights into the GABAA receptor gating cycle
… receptors. Lastly, I will also demonstrate how positive allosteric modulators alter the gating landscape and how the general anaesthetic propofol can directly activate the receptor. This work provides a new structural and mechanistic framework to explore and interpret the action of …
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Examining the Roles of GABAA Receptor Subtypes in Anxiety and Anxiolysis: Focusing on the Basolateral Amygdala
… selective and non-selective GABA<sub>A</sub>R positive allosteric modulators (PAMs) both in wild type mice and in mutant mice that express BZ-insensitive GABA<sub>A</sub>Rs of specific <em>α-subtypes</em>.</p> <p>In our experiments, systemic injections of the<em> <em>α1</em>-<em>selective PAM …
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THE MECHANISMS AND PHARMACOLOGY OF NEURONAL NICOTINIC ACETYLCHOLINE RECEPTORS IN THE CENTRAL NERVOUS SYSTEM
… avoided by using a novel class of drugs; type-II positive allosteric modulators of α7 nAChRs (α7-PAMs) such as PNU-120596 (i.e., PNU). At physiological levels, choline alone is ineffective as an α7 agonist because of its low concentration in the cerebrospinal fluid (~10 µM) and low potency for α7 …
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Investigating the role of AMPAkines in an animal model of post-traumatic stress disorder (PTSD)
… and of the potential value of glutamate receptor modulators in treating the disorder. Stress-related elevation in glutamate exerts detrimental effects on cognition, especially via activation of the N-methyl-D-aspartate (NMDA) receptor, and has been implicated in PTSD associated cognitive deficits. …
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Endogenous neurosteroid actions at GABAA receptors during neuronal development
… 5a-pregnan-3a-ol-20-one (5a3a) are potent positive allosteric modulators of GABAAR function - a property that endows these steroids with anxiolytic, sedative and anti-convulsant actions. Importantly, in addition to importing steroids from the periphery, the brain also harbours a …
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Modulación molecular de la función del receptor neuronal α7
… α7 por moduladores alostéricos positivos (PAMs, positive allosteric modulators) a concentraciones del orden nanomolar o micromolar bajo; iv) La reducción de la potenciación causada por los péptidos β-Amiloide no es específica del tipo de modulador alostérico positivo. Estos resultados demuestran …
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Repeated Zolpidem Treatment Effects on Sedative Tolerance, Withdrawal, mRNA Levels, and Protein Expression
… action of gamma-Aminobutyric acid (GABA) by allosterically binding to GABAA receptors (GABAAR). Prolonged use of GABAAR positive allosteric modulators (PAM) can lead to behavioral tolerance, the diminished response to the same drug dose with repeated use, and withdrawal, a group of symptoms …