Honors Theses
Date of Award
2018
Document Type
Undergraduate Thesis
Department
Pharmaceutics and Drug Delivery
First Advisor
John Rimoldi
Relational Format
Dissertation/Thesis
Abstract
Major Depressive Disorder, colloquially known as depression, is a devastating mental illness that affects a large portion of today's population. Following a drug side-effect that caused depression, the monoamine theory of depression was created, stating that depressive symptoms were caused by a decrease in concentrations of vital monoamine neurotransmitters at the synaptic cleft. Pharmaceutical remedies to combat depression were first introduced in the 1950s and to this date, most available drugs follow the monoamine theory. These drugs have a large loading dose lag time, numerous negative side effects, and still many patients do not experience relief from symptoms. In 2000, the Stress-neurogenic theory was proposed, suggesting depressive symptoms decreased neurogenesis and dendritic retraction, induced by excess cortisol from chronic stress. This new theory opened the door for further studies to be conducted on possible pharmacotherapies for MDD. Ketamine had shown some antidepressant effects, but was not a sufficient option due to the dissociative effects and history of abuse. Further studies were done to indicate that ketamine's antidepressant effects were caused by the metabolite (2R,6R)-hydroxynorketamine and that the mechanism of action seems to be NMDA receptor independent. The goal of this thesis was to construct an efficient complete synthesis pathway of (2R,6R)- hydroxynorketamine from commercially available chemicals. This was done by evaluating chemically and structurally similar reactions that had been previously published to piece together a new synthesis of (2R,6R)-HNK. The product of this research will be sent to a partnering lab for further studies to be completed on the NMDA-independent and possibly AMPA receptor-dependent mechanism by which ketamine exhibits such promising antidepressant effects. Further understanding of this mechanism brings us one step closer to better future pharmacotherapies for MDD.
Recommended Citation
Fairley, Savannah, "Synthesis of (2R,6R)-Hydroxy-norketamine for Evaluation of Antidepressant Effects" (2018). Honors Theses. 839.
https://egrove.olemiss.edu/hon_thesis/839
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