Defense Date

2019

Document Type

Thesis

Degree Name

Master of Science

Department

Physiology and Biophysics

First Advisor

Jose M. Eltit

Second Advisor

Paul Dent

Third Advisor

Charles D. Anderson

Abstract

In humans and other organisms, monoaminergic systems are crucial in neuronal function and behavior. The monoamine transporters (MATs), which can be found on the presynaptic plasma membrane of neurons in the central nervous system (CNS), are crucial in the regulation of neurotransmitter concentration in the synaptic cleft. As the duration and concentration of neurotransmitters in the cleft affect further downstream signaling responses, these proteins are important targets for both understanding neuronal physiology and compounds of interest. Multiple theories exist proponing the contribution of MATs to a variety of mental and neurological disorders, including depression. This theory establishes that depression is caused by imbalances in monoamine neurotransmitters. Compounds such as Fluoxetine (FLX) are classified as selective serotonin reuptake inhibitors (SSRIs), these drugs selectively block the reuptake of neurotransmitters at the serotonin transporter (SERT). Since differences in MAT selectivity of inhibitory compounds are influential to selecting efficacious antidepressant treatments, we utilized a unique fluorescent analysis technique to explore three therapeutic compounds of interest (in-vitro) which contain structural similarity to FLX. Our results confirm the selectivity of FLX at SERT, and classify the novel compounds studied into different potential categories of reuptake inhibitors. We hope these compounds will be studied further to elucidate their potentially therapeutic roles and mitigation of undesired side effects seen in other medications.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

7-20-2019

Available for download on Thursday, July 18, 2024

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