Synthesis and structural modification of the MDMA antagonist nantenine: A naturally occurring aporphine alkaloid
Item
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Title
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Synthesis and structural modification of the MDMA antagonist nantenine: A naturally occurring aporphine alkaloid
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Identifier
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d_2009_2013:765895d078f0:10616
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identifier
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10788
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Creator
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Le Gendre, Onica,
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Contributor
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Wayne W. Harding
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Date
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2010
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Language
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English
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Publisher
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City University of New York.
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Subject
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Organic chemistry | Antagonist | Aporphine | MDMA | Nantenine | Synthesis
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Abstract
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MDMA ("Ecstasy") is a synthetic phenethylamine stimulant which is known to affect the re-uptake of serotonin, dopamine and nor-epinephrine in the brain. Adverse effects of "Ecstasy" in humans include development of hyperthermia, hallucinations, organ failure and in extreme cases, death. There is evidence that the behavioral and physiological effects of MDMA are mediated by alpha1-adrenergic and 5-HT2A receptors. Nantenine is a naturally occurring aporphine alkaloid which has been shown to block and reverse behavioral and physiological effects of MDMA in mice via antagonism of the aforementioned receptors. However, the relative role of these receptors in mediating the MDMA antagonizing effects of nantenine in vivo is unknown.;The goal of this project is to explore different methods of synthesizing nantenine and nantenine derivatives. These compounds were subjected to in vitro testing for antagonistic activity at alpha1-adrenergic and 5-HT2A receptors and their ability to block/reverse MDMA-induced effects in mice through in vivo drug discrimination assays. This work provided insight into the relative role of these receptors in mediating the antagonistic activity of nantenine. Moreover, the results may provide the foundation for the design and development of potent and selective MDMA antagonists in the future.;Here we present our synthetic studies as well as the results of biological evaluations of nantenine and analogues.
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Type
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dissertation
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Source
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2009_2013.csv
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degree
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Ph.D.
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Program
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Chemistry
