Graduate Thesis Or Dissertation

 

The Synthesis of Unnatural Morphine Derivatives as Glial Activation Inhibitors and The Synthesis of Corticosterone-Glucuronide Public Deposited

https://scholar.colorado.edu/concern/graduate_thesis_or_dissertations/xk81jk89r
Abstract
  • A novel, non-neuronal mechanism to explain the development of opioid tolerance and dependance has been described. This mechanism involves the activation of spinal cord glia. Glia are important contributors to the creation of enhanced pain states via the release of neuroexcitatory and proinflammatory substances. Data suggest that glia also release neuroexcitatory substances in response to morphine, thereby opposing its effects. Inhibiting glial activation could therefore increase the clinical utility of analgesic drugs. The synthesis of advanced intermediates for the development of a series of novel morphinan-like structures that are potential glial activation inhibitors will be discussed. Corticosterone displays an intense immunosuppressive effect at the time of delivery; however, recent work has shown that it produces dramatic glial activation and a pro-inflammatory response later in time. Corticoserone is glucuronidated in its metabolic pathway. Corticosterone-glucuronide (CortG) was synthesized to test whether the glucuronidation is the cause of the eventual pro-inflammatory effects.
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  • 2010
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  • 2019-11-18
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