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Kinetics And Mechanism Of S-Nitrosation And Oxidation Of Cysteamine By Peroxynitrite, Wilbes Mbiya
Kinetics And Mechanism Of S-Nitrosation And Oxidation Of Cysteamine By Peroxynitrite, Wilbes Mbiya
Dissertations and Theses
Cysteamine (CA), which is an aminothiol drug medically known as Cystagon® was studied in this thesis. Cysteamine was reacted with a binary toxin called peroxynitrite (PN) which is assembled spontaneously whenever nitric oxide and superoxide are produced together and the decomposition of peroxyinitrite was monitored. PN was able to nitrosate CA in highly acidic medium and excess CA to form S-nitrosocysteamine (CANO) in a 1:1 with the formation of one mole of CANO from one mole of ONOOH. In excess oxidant (PN) the following 1:2 stoichiometric ratio was obtained; ONOO- + 2CA → CA-CA + NO2- + H …
Developing Thyronamine Analog Pharmaceuticals Targeting Taar1 To Treat Methamphetamine Addiction, Troy Andrew Wahl
Developing Thyronamine Analog Pharmaceuticals Targeting Taar1 To Treat Methamphetamine Addiction, Troy Andrew Wahl
Dissertations and Theses
As a part of the overall program in the Grandy laboratory at Oregon Health & Science University (OHSU), studying the underlying chemical biology of methamphetamine (Meth) addiction, this dissertation reports on the development of six new thyronamine analogs which were synthesized and assayed against trace amine associated receptor 1 (TAAR1), giving preliminary results consistent with the analogs being inverse agonists. Due to highly variable TAAR1 expression levels in the assays, based on inter-assay response to control Meth stimulation as well as other possible factors, kinetic models were developed to qualitatively explain the assay results. The models set approximate limits on …