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Targeting The Γ-Aminobutyric Acid A Receptor (Gabaar) To Alleviate Inflammation For Asthma And Neuropathic Pain, Amanda Nicole Nieman

Theses and Dissertations

The γ-Aminobutyric Acid A Receptor (GABAAR) is a ligand-gated, pentameric chloride channel composed of subunits that include α1-6, β1-3, γ1-3, δ, ε, π, θ, ρ1-3.1-2 The most common arrangement includes two α subunits, two β subunits, and a γ subunit.3 This receptor includes two binding sites for the endogenous ligand γ-aminobutyric acid (GABA) between the α and β subunits and a binding site between the α and γ subunit for benzodiazepines, a large family of positive allosteric modulators.4-5

Benzodiazepines are one of the most prescribed classes of pharmaceuticals to treat anxiety, insomnia, and epilepsy as well as for muscle relaxation.6-7 …

Design And Synthesis Of Achiral And Chiral Imidazodiazepine (Imdz) Gaba(A)R Subtype Selective Ligands For The Treatment Of Cns Disorders, As Well As Asthma, Guanguan Li

Theses and Dissertations

Gamma-aminobutyric acid type A receptors (GABAAR) are transmembrane pentameric ligand-gated chloride ion channels that respond to GABA, the major inhibitory neurotransmitter in the central nervous systems (CNS). The benzodiazepines (BZDs) bind at the extracellular interface of the α+γ2-subunits of GABAAR. The binding of ligands at different subunits of GABAA receptors specifically at α1-6β2/3 γ2 ion channels, can affect a wide variety of brain functions. The α1-subtype selective ion channels of GABAARs are involved in the sedative, ataxic, amnesic, anticonvulsant and addictive effects, which should be avoided, with the exception of the anticonvulsant effects, when designing ligands for this BZ allosteric …

Part I: Design And Synthesis Of Novel Drugs To Treat Asthma By Targeting Gabaa Receptors In The Lung Part Ii: Design And Synthesis Of Novel Α2/Α3 Subtype Selective Gabaar Ligands For Cns Disorders, Rajwana Jahan

Theses and Dissertations

Part I. Asthma is a major healthcare challenge affecting an estimated 300 million people globally. Over $56 billion in asthma-related healthcare expenses occur in the United States annually. Moreover, asthma accounts for the majority of missed school/work days, Doctor and emergency room visits, and patient hospitalizations in young persons. Consequently, asthma continues to be a significant healthcare burden in terms of morbidity, productivity, and medical costs. Beta 2-adrenergic agonists and inhaled corticosteroids (ICs) are the most commonly prescribed treatments for the acute and chronic management of asthma. Both agents present efficacy, compliance, and adverse side effect concerns.

Hence, there is …