Date of Award
Chemistry and Biochemistry
Major Depressive disorder (MDD) plagues society and stands at the forefront of research as MDD affects approximately 16% of the population. Pharmaceutical drugs, including the selective serotonin reuptake inhibitors (SSRIs), have been used for MDD treatment and remain a popular option today. However, current antidepressant treatments have proven to be ineffective in just less than half of the patients. Research continues with the goal to better understand the mechanisms of the pathology of depression and to search for other treatment options. For example, the stress-neurogenesis hypothesis investigates the role of stress and decreased neuroplasticity within MDD.
Supporting the stress-neurogenesis hypothesis, the well-known anesthesia drug, ketamine, has shown antidepressant effects linked to glutamate neurotransmission and the successive downstream effects. However, the positive effects sustain after the rapid hepatic metabolism of ketamine leading scientists to explore key metabolites of ketamine and their effects on depressive symptoms.
One of the ketamine metabolites, (2R, 6R)-hydroxynorketamine (HNK), has shown clinical benefits while decreasing the adverse side effects of ketamine in treatment-resistant MDD. The aim of this thesis research is to explore a simple oxidation protocol for the direct synthesis of hydroxynorketamine from the precursor compound norketamine.
Patrick, Ann K., "Approaches Towards the Synthesis of Ketamine Metabolites" (2020). Honors Theses. 1327.