Current Search: info:fedora/islandora:personCModel (x) » Miami (Fla.) (x) » thesis (x) » McDonald, Patricia (x)
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Title
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Development of cell-based functional assays to identify and characterize novel GABAb receptor allosteric modulators.
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Creator
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Aitken, Maria de Lourdes, McDonald, Patricia, Quintyne, Nicholas, Harriet L. Wilkes Honors College
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Abstract/Description
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Dysfunction of GABAB-receptor (GABAB-R)-mediated synaptic transmission underlies various nervous system disorders including epilepsy, depression, schizophrenia, and addiction. Currently, only one GABAB-R orthosteric ligand is in clinical use. However, side effects such as sedation, tolerance, and motor impairment limit its use. A dissociation of the therapeutic effects from the side effects may be achievable with drugs enhancing the endogenous physiological cellular response. The development...
Show moreDysfunction of GABAB-receptor (GABAB-R)-mediated synaptic transmission underlies various nervous system disorders including epilepsy, depression, schizophrenia, and addiction. Currently, only one GABAB-R orthosteric ligand is in clinical use. However, side effects such as sedation, tolerance, and motor impairment limit its use. A dissociation of the therapeutic effects from the side effects may be achievable with drugs enhancing the endogenous physiological cellular response. The development of GABAB-R allosteric modulators has provided new modes of efficacy that may facilitate the development of novel therapeutic agents. In the present study, we investigated the effects of novel, newly synthesized GABAB-R allosteric ligands using a HEK-293 cell line stably expressing human GABAB1(b)/human GABAB(2) subunits using a cell-based cAMP HTRF assay. One compound was identified and characterized as a potential novel GABAB-R positive allosteric modulator (PAM), and will be subjected to further in vitro and in vivo analyses.
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Date Issued
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2013
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PURL
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http://purl.flvc.org/fau/fd/FA00003502
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Format
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Document (PDF)
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Title
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In Vivo Characterization of a Novel GLP-1R Biased Agonist.
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Creator
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Turn, Rachel, McDonald, Patricia, Kirchman, Paul, Harriet L. Wilkes Honors College
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Abstract/Description
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In the twenty-first century one of the most widespread and challenging human disorders is Type 2 Diabetes Mellitus (T2DM). Standard therapies are effective in achieving glycemic control but have undesired side effects, such as hypoglycemia and weight gain. As a result, there is an urgent need to develop novel therapeutics to treat this devastating disease. The Glucagon-like peptide receptor (GLP-1R) plays a critical role in glucose homeostasis and is therefore an attractive target for...
Show moreIn the twenty-first century one of the most widespread and challenging human disorders is Type 2 Diabetes Mellitus (T2DM). Standard therapies are effective in achieving glycemic control but have undesired side effects, such as hypoglycemia and weight gain. As a result, there is an urgent need to develop novel therapeutics to treat this devastating disease. The Glucagon-like peptide receptor (GLP-1R) plays a critical role in glucose homeostasis and is therefore an attractive target for treatment of T2DM. GLP-1R exhibits pleiotropic signaling, so to determine if activation of one signaling pathway to the exclusion of others will provide improved therapeutics, we sought to identify GLP-1R biased ligands. Screening of large lentivirus-encoded combinatorial peptide libraries identified a novel GLP-1R ligand (peptide SR) exhibiting functional selectivity. Here, we describe the in vitro and in vivo pharmacological characterization of peptide SR and highlight the differences observed between this treatment and the reference ligand, Exendin-4.
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Date Issued
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2015
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PURL
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http://purl.flvc.org/fau/fd/FA00003660
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Format
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Document (PDF)
