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Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto Feb 2024

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …


Synthesis And Evaluation Of C-10 Nitrogenated Aporphine Alkaloids At Serotonin And Dopamine Receptors, Anupam Karki Jun 2021

Synthesis And Evaluation Of C-10 Nitrogenated Aporphine Alkaloids At Serotonin And Dopamine Receptors, Anupam Karki

Dissertations, Theses, and Capstone Projects

Aporphine alkaloids, belonging to the isoquinoline class of compounds, have been investigated as a potential source of ligands for Central Nervous System (CNS) receptors. Previous research indicates that the aporphine scaffold may be manipulated to synthesize selective ligands for serotonin and dopamine receptors. Novel aporphine alkaloids containing C10 nitrogen substitutions were synthesized, and their affinities were evaluated at serotonin (5-HT1A, 5-HT1B, 5-HT2A, 5-HT7A) receptors and dopamine (D1, D2, D3, D4, and D5) receptors. Two series of racemic aporphine compounds with C10 nitrogenous functionalities were synthesized and analyzed at the aforementioned receptors. The first series of aporphine alkaloids contain C10 nitro, …