Date Approved

6-21-2021

Embargo Period

6-23-2021

Document Type

Thesis

Degree Name

M.S. Pharmaceutical Sciences

Department

Chemistry and Biochemistry

College

College of Science & Mathematics

Advisor

Thomas M. Keck, Ph.D.

Committee Member 1

Kandalam Ramanujachary, Ph.D.

Committee Member 2

Subash Jonnalagadda, Ph.D.

Keywords

D2 receptor ligands, Prepulse inhibition, morphine, MP-III-024, dopamine D2 drugs

Subject(s)

Drugs--Design; Niemann-Pick diseases--Treatment

Disciplines

Medicinal and Pharmaceutical Chemistry

Abstract

This thesis work includes three projects. First part deals with the investigation of novel D2 receptor ligands in Prepulse inhibition. The goal of this study is to establish a relationship between dopamine receptor antagonists and agonists and prepulse inhibition which can then serve as a working model for an in-vivo efficacy of novel dopamine D2 drugs. The second part of the thesis work deals with Niemann pick disease type C. Niemann pick disease type C is a progressive genetic disorder that is characterized by the lysosomal accumulation of lipids which causes neurodegeneration, dementia, ataxia, and death. NPC1nmf164 mutant mice (knockout) have a delayed acquisition of motor skills during development. The aim of our study was to identify cellular and molecular pathways involved in causing and progressing NPC in young patients from which effective therapeutic interventions can be designed and tested to prevent or delay the onset of the disease and prolong and improve the quality of life of young NPC patients. Finally, the last part of this thesis work includes studies on synergistic anithyperalgesic and antinociceptive effects of morphine and MP-III-024, a positive allosteric modulator at α2GABAA and α3GABAA receptors. The purpose of this study was to examine the interactive effects of the μ-opioid agonist morphine and the α2GABAA and α3GABAA receptor positive allosteric modulator MP-III-024 in preclinical models of mechanical hyperalgesia and thermal nociception.

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