Investigate the Dopaminergic Neurotoxicity Profile of Designer Drugs (Piperazine Derivatives) by Mohammed Almaghrabi a Thesis Su
Investigate the dopaminergic neurotoxicity profile of designer drugs (Piperazine derivatives) by Mohammed Almaghrabi A thesis submitted to the Graduate Faculty of Auburn University in partial fulfillment of the requirements for the Degree of Master of Science Auburn, Alabama 8/4/2018 Keywords: designer drugs, N27 cell, oxidative stress, mitochondrial dysfunction, neurotoxicity Copyright 2018 by Mohammed Almaghrabi Approved by Muralikrishnan Dhanasekaran, Co-chair, Professor of Pharmacology Randall Clark, Co-chair, Professor of Medicinal Chemistry Jack Deruiter, Professor of Medicinal Chemistry Vishnu Suppiramaniam, Professor of Pharmacology Abstract Different botanical derived, or synthetic addictive substances have been “misused” and/or “abused” for centuries around the world. To overcome the abuse by these substances, strict legal laws were constituted globally. However, novel and drugs with chemical structures similar to illegal psychoactive drugs substances (with a slight structural change) were manufactured in undercover laboratories to have the same or augmented psychostimulatory effects. Currently, the major classes of designer drugs are piperazines, cathinones, synthetic cannabinoids, synthetic opioids, tryptamines, and phenethylamines. These classes of designer drugs have shown to elicit significant psychostimulatory effect by a different mechanism of action. There are very few reports on the dopaminergic neurotoxicity of piperazine derivatives. However, they have shown to affect various monoaminergic neurotransmission. In the current study, we have synthesized and elucidated the neurotoxic mechanisms of new piperazines. ii Acknowledgments In the name of Alláh, the most Gracious, and the most merciful, I praise him for his reconcile and guidance. Behind this work a lot of supportive people who helped and encourage me to achieve this step of education. First, I would like to thank my advisor Dr.
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