Medicine and Health Sciences Commons^™

Design, Synthesis And Pharmacological Characterization Of Potential Mu Opioid Receptor Selective Ligands, Abhishek S. Kulkarni

Theses and Dissertations

Selective Mu Opioid Receptor (MOR) antagonists possess immense potential in the treatment of opioid abuse/addiction. Utilizing the “message-address” concept, our laboratory reported a novel, reversible, non-peptide MOR selective antagonist 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4՛-pyridyl)carboxamido]morphinan (NAP). Molecular modeling studies revealed that the selectivity of NAP for the MOR is because of a π-π stacking interaction of its pyridine ring with the Trp318residue in theMOR. Pharmacological characterization showed that NAP is a P-glycoprotein substrate, thereby limiting its use in the treatment of opioid abuse/addiction. Thus, to modify NAP, we replaced the pyridine ring with its isosteric counterpart thiophene. Isosteric replacement …

Structure-Activity Relationship Studies Of Synthetic Cathinones And Related Agents, Rachel A. Davies

Theses and Dissertations

Synthetic cathinones and related agents represent an international drug abuse problem, and at the same time an important class of clinically useful compounds. Structure-activity relationship studies are needed to elucidate molecular features underlying the pharmacology of these agents. Illicit methcathinone (i.e., MCAT), the prototype of the synthetic cathinone class, exists as a racemic mixture. Though the differences in potency and target selectivity between the positional and optical isomers of synthetic cathinones and related agents have been demonstrated to have important implications for abuse and therapeutic potential, the two MCAT isomers have never been directly compared at their molecular targets: the …

Diuretic, Natriuretic, And Vasodepressor Activity Of A Lipid Fraction Enhanced In Medium Of Cultured Mouse Medullary Interstitial Cells By A Selective Faah Inhibitor, Zdravka P. Daneva

Theses and Dissertations

The relationship between the endocannabinoid system in the renal medulla and the long-term regulation of blood pressure is not well understood. To investigate the possible role of the endocannabinoid system in renomedullary interstitial cells, mouse medullary interstitial cells (MMICs) were obtained, cultured and characterized for their responses to treatment with a selective inhibitor of fatty acid amide hydrolase (FAAH), PF-3845. Treatment of MMICs with PF-3845 increased cytoplasmic lipid granules detected by Sudan Black B staining and multilamellar bodies identified by transmission electron microscopy. HPLC analyses of lipid extracts of MMIC culture medium revealed a 205nm-absorbing peak that showed responsiveness to …

National And Local Antibiotic Prescribing Trends And Prescribing Appropriateness In Older Adults, Fawaz M. Alotaibi

Theses and Dissertations

Background: Antibiotic overuse/misuse has been documented in several reports to increase the risk of Clostridioides difficile (C.diff) infection and antibiotic resistance. The older adult population is more prone to use antibiotic medications than any other age group due to decreased immune function, use of urinary catheters, ventilation during hospitalization and other factors. Antibiotic resistance and C.diff are major public health problems. However, studies examining the trends of antibiotic use and the association between the antibiotic use and negative health outcomes among older adults in the outpatient and emergency department settings are limited.

Objectives: The main objectives of this …

Understanding Medication Self-Management Capacity Among Older Adults Living In Low-Income Housing Communities, Amal M. Badawoud

Theses and Dissertations

Understanding Medication Self-Management Capacity among Older Adults Living in Low-Income Housing Communities

ABSTRACT

Background: Medication self-management capacity (MMC) is an individual’s cognitive and functional ability to self-administer a medication regimen as prescribed. Poor MMC is an issue in older adults often resulting in negative health outcomes and loss of independence. Therefore, understanding low-income older adults’ capacity to manage their medications may help identify individuals who are at risk for developing medication mismanagement and guide future intervention strategies based on an individual need to promote safe medication use and healthy aging in place in the community.

Objectives: 1) To determine the …

Development Of Bivalent Ligands Targeting The Putative Mu Opioid Receptor And Chemokine Receptor Cxcr4 Heterodimer, Bethany A. Reinecke

Theses and Dissertations

Human immunodeficiency virus (HIV) and opioid abuse have been described as synergistic epidemics. Pharmacologically, it has been found that opioids have the capacity to enhance HIV infection and replication. Research has shown that activation of the mu-opioid receptor (MOR) elevates the expression of the HIV-1 entry co-receptor CXCR4 on T-lymphocytes in the peripheral nervous system, thus allowing for enhanced viral entry and invasion. Although the exact mechanism for opioid modulation of CXCR4 expression and subsequent exacerbation of HIV is unknown, several hypotheses exist. One hypothesis is that MOR and CXCR4 are functionally interacting through the formation of a heterodimer. This …