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Enhanced Analgesic ...
Enhanced Analgesic Effects and Gastrointestinal Safety of a Novel, Hydrogen Sulfide-Releasing Anti-Inflammatory Drug (ATB-352) : A Role for Endogenous Cannabinoids
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Costa, Soraia K. P. F. (författare)
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Muscara, Marcelo N. (författare)
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Allain, Thibault (författare)
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Dallazen, Jorge (författare)
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Gonzaga, Larissa (författare)
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Buret, Andre G. (författare)
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Vaughan, David J. (författare)
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- Fowler, Christopher J (författare)
- Umeå universitet,Institutionen för farmakologi och klinisk neurovetenskap
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de Nucci, Gilberto (författare)
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Wallace, John L. (författare)
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(creator_code:org_t)
- Mary Ann Liebert, 2020
- 2020
- Engelska.
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Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert. - 1523-0864 .- 1557-7716. ; 33:14, s. 1003-1009
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://www.liebertp...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Aims: The covalent linking of nonsteroidal anti-inflammatory drugs to a hydrogen sulfide (H2S)-releasing moiety has been shown to dramatically reduce gastrointestinal (GI) damage and bleeding, as well as increase anti-inflammatory and analgesic potency. We have tested the hypothesis that an H2S-releasing derivative of ketoprofen (ATB-352) would exhibit enhanced efficacy without significant GI damage in a mouse model of allodynia/hyperalgesia.Results: ATB-352 was significantly more potent and effective as an analgesic than ketoprofen and did not elicit GI damage. Pretreatment with an antagonist of the CB1 cannabinoid receptor (AM251) significantly reduced the analgesic effects of ATB-352. The CB1 antagonist exacerbated GI damage when coadministered with ketoprofen, but GI damage was not induced by the combination of ATB-352 and the CB1 antagonist. In vitro, ATB-352 was substantially more potent than ketoprofen as an inhibitor of fatty acid amide hydrolase, consistent with a contribution of endogenous cannabinoids to the analgesic effects of this drug. Blood anandamide levels were significantly depressed by ketoprofen, but remained unchanged after treatment with ATB-352.Innovation: Ketoprofen is a potent analgesic, but its clinical use, even in the short term, is significantly limited by its propensity to cause significant ulceration and bleeding in the GI tract. Covalently linking an H2S-releasing moiety to ketoprofen profoundly reduces the GI toxicity of the drug, while boosting analgesic effectiveness.Conclusion: This study demonstrates a marked enhancement of the potency and effectiveness of ATB-352, an H2S-releasing derivative of ketoprofen, in part, through the involvement of the endogenous cannabinoid system. This may have significant advantages for the control and management of pain, such as in a postoperative setting.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- inflammation
- pain
- hydrogen sulfide
- ulcer
- analgesic
- ketoprofen
- cannabinoid
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Costa, Soraia K. ...
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Muscara, Marcelo ...
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Allain, Thibault
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Dallazen, Jorge
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Gonzaga, Larissa
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Buret, Andre G.
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visa fler...
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Vaughan, David J ...
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Fowler, Christop ...
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de Nucci, Gilber ...
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Wallace, John L.
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visa färre...
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Antioxidants and ...
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Umeå universitet