• Login
    View Item 
    •   Home
    • UA Graduate and Undergraduate Research
    • UA Theses and Dissertations
    • Dissertations
    • View Item
    •   Home
    • UA Graduate and Undergraduate Research
    • UA Theses and Dissertations
    • Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UA Campus RepositoryCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournalThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournal

    My Account

    LoginRegister

    About

    AboutUA Faculty PublicationsUA DissertationsUA Master's ThesesUA Honors ThesesUA PressUA YearbooksUA CatalogsUA Libraries

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Studies on opioid delta receptor mediated antinociception, opioid antinociceptive tolerance and physical dependence

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    azu_td_9729461_sip1_m.pdf
    Size:
    5.133Mb
    Format:
    PDF
    Download
    Author
    Bilsky, Edward James, 1967-
    Issue Date
    1997
    Keywords
    Biology, Neuroscience.
    Health Sciences, Pharmacology.
    Biology, Animal Physiology.
    Advisor
    Porreca, Frank
    
    Metadata
    Show full item record
    Publisher
    The University of Arizona.
    Rights
    Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
    Abstract
    The central hypothesis of this dissertation is that agonists and antagonists acting at the delta opioid receptor will have therapeutic applications in treating acute and chronic pain states and in the treatment of drug addiction. It is further hypothesized that delta compounds will have better therapeutic profiles than currently available opioids that act predominantly at the mu receptor. In advancing the central hypothesis, selective nonpeptidic delta compounds, that readily cross the blood brain barrier after systemic administration, were tested. BW373U86, a nonpeptidic ligand with moderate selectivity and activity at delta opioid receptors represented a lead compound. A structurally related molecule, SNC80, displayed an improved selectivity and activity profile compared to BW373U86. Importantly, SNC80 produced antinociception following systemic administration which was blocked by delta, but not mu, selective antagonists. The pharmacology of delta opioid receptors was further studied using antisense oligodeoxynucleotides that disrupted the synthesis of delta receptors in vivo and in vitro. The experiments provided further evidence for distinct delta receptor subtypes and demonstrated the utility of the antisense approache in studying neurochemical processes in vivo. Several studies addressed the phenomenon of opioid tolerance and physical dependence, two processes which compromise the clinical application of currently available opioid analgesics. The observation that NMDA receptor antagonists block the development of antinociceptive tolerance to repeated administrations of morphine was confirmed. The results were extended by demonstrating that NMDA antagonists did not block antinociceptive tolerance to more selective delta or mu agonists. These studies caution against the generalization that an effect seen with morphine is applicable to all opioid agonists. Further hypotheses regarding the mechanisms of opioid tolerance and physical dependence were tested using inhibitors of protein kinases and putative neutral and inverse opioid antagonists. These studies advanced the hypothesis that opioid receptor phosphorylation may play a critical role in the development of opioid antinociceptive tolerance and physical dependence. In summary, this dissertation has provided strong evidence that nonpeptidic delta selective opioid agonists and antagonists can be developed and that these compounds will have therapeutic applications in the treatment of pain and addictive disorders.
    Type
    text
    Dissertation-Reproduction (electronic)
    Degree Name
    Ph.D.
    Degree Level
    doctoral
    Degree Program
    Graduate College
    Pharmacology & Toxicology
    Degree Grantor
    University of Arizona
    Collections
    Dissertations

    entitlement

     
    The University of Arizona Libraries | 1510 E. University Blvd. | Tucson, AZ 85721-0055
    Tel 520-621-6442 | repository@u.library.arizona.edu
    DSpace software copyright © 2002-2017  DuraSpace
    Quick Guide | Contact Us | Send Feedback
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.