Date of Award

1-1-2012

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Chemistry

Content Description

1 online resource (x, 124 pages) : illustrations (some color)

Dissertation/Thesis Chair

Li Niu

Committee Members

Jayanti Pande, Alexander Shekhtman, Carla Theimer

Keywords

2, 3-benzodiazepine, ALS, AMPA receptor, antagonist, electrophysiology, glutamate receptor, Glutamic acid, Benzodiazepines

Subject Categories

Biochemistry | Chemistry | Neuroscience and Neurobiology

Abstract

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are one of the three subtypes of ionotropic glutamate receptors. AMPA receptors mediate fast synaptic neurotransmission in the central nervous system (CNS). Over-activation of calcium permeable AMPA receptors causes intracellular calcium overload, which leads to neurodegeneration and cell death. As such, AMPA receptors have been implicated in a number of neurological disorders and diseases, such as epilepsy, amyotrophic lateral sclerosis (ALS), and Parkinson's disease. 2,3-Benzodiazepine derivatives (or GYKI compounds) are a group of structurally similar compounds synthesized as inhibitors of AMPA receptors, and they have been used as potential drug candidates for the treatment of various neurological disorders involving excessive activity of AMPA receptors. However, the detailed mechanism of action of these inhibitors has not been well understood, and a structure-activity relationship has not been defined at the molecular level.

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