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Synthesis and Evaluation of Dual-Acting Ligands for Mu Opioid And Neuropeptide FF Receptors
Başlık:
Synthesis and Evaluation of Dual-Acting Ligands for Mu Opioid And Neuropeptide FF Receptors
Yazar:
McPherson, Kelsey G., author.
ISBN:
9780438067561
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (460 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Advisors: John M. Rimolid; Christopher R. McCurdy Committee members: David A. Colby; David C. Stevens.
Özet:
Pain, although subjective, is an unpleasant sensation caused by a noxious stimulus, that effects millions of people every year. Currently, the most frequently prescribed class of analgesics for moderate to severe acute and sometime chronic pain are opioid analgesics, most commonly ?-opioid receptor (MOP) agonists, such as oxycodone, morphine, and fentanyl. Although these drugs provide significant pain relief, they are also associated with unwelcome side effects such as constipation, addiction, physical dependence, respiratory depression, and physiological tolerance that leads to hyperalgesia. Receptor desensitization due to excessive receptor activation by an agonist is but one source of physiological tolerance; it can also develop through the activation of homeostasis-regulating endogenous anti-opioid systems. One of these anti-opioid systems, the neuropeptide FF (NPFF) system, which is comprised of two receptor subtypes NPFF1 and NPFF2, is a member of the RFamide family and has been shown to modulate opioid activity. Although, currently, there are limited numbers of reported NPFFR ligands, it has been indicated that antagonism of NPFFR leads to the attenuation of physiological tolerance. Currently, many of these ligands are peptidic in structure and are not considered ideal candidates for drug development. However, the design and synthesis of small molecule, dual-acting ligands that act as MOP agonists and NPFF antagonists are a viable approach to opioid analgesics. These ligands would provide the necessary opportunity to provide analgesia, while also blocking a physiological tolerance development center, thus preventing the development of hyperalgesia as well as provide an opioid drug class with reduced side effect liabilities.
Notlar:
School code: 0131
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(691790.1) | 691790-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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