Medicinal and Pharmaceutical Chemistry Commons^™

Computational Design Of Β-Fluorinated Morphine Derivatives For Ph-Specific Binding, Makena Augenstein, Nayiri Alexander, Matthew Gartner

Student Scholar Symposium Abstracts and Posters

Molecular extension and dissection techniques are used to design a morphine derivative that promotes selective binding in inflamed tissue due to its lower pH while avoiding dangerous activation in the brain. Morphine is used to treat pain associated with inflammation. While being effective analgesics, opioids carry the risk of central side effects, including addiction, respiratory depression, and sedation. Opioids are agonists that bind to the μ-opioid peptide receptor (MOR) within central and peripheral nerves and act via a G-protein coupled receptor pathway.

Deprotonation of the tertiary amine induces a negative charge on the nitrogen, discouraging binding at physiological pH (pH=7.4). …

Compounded Gabapentin For Felines: Associated Metabolic Processes And Analysis Of Potency, Johnny Altwal

Student Scholar Symposium Abstracts and Posters

Pharmaceutical compounding provides pharmacists and clinicians the opportunity to create unique drug formulations that are better suited to a specific patient’s needs. This is especially prevalent in veterinary medicine where clinicians treat a variety of maladies in a large number of species, thereby requiring unique formulations to more easily deliver drugs to animals. Several examples of compounded veterinary formulations with sub-therapeutic potencies have been published, but none examine compounded gabapentin. Gabapentin is frequently compounded into an oral suspension for veterinary use from tablets or capsules for the purpose of pain management in felines and other small animals. The project’s goals …

Computational Design Of Β-Fluorinated Morphine Derivatives For Ph-Specific Binding, Nayiri Alexander, Makena Augenstein, Angelina Sorensen, Matthew Gartner

Student Scholar Symposium Abstracts and Posters

Opioids such as morphine are important pain-relieving drugs but also carry a risk of harmful side effects including addiction. Morphine is active in both healthy and inflamed tissue, however, decreasing the pKa of the biochemically-active amine group can promote selective binding in the more acidic conditions of inflamed tissue and reduce harmful side effects associated with opioids. Herein, we explore the impact of fluorination on the pKa of fluoromorphine derivatives to identify which will bind selectively in inflamed tissue. Theoretical pKa values are determined at the M06-2X(SMD)/aug-cc-pVDZ level of theory to calculate the ΔGaq" …