| Comparison of the antinociceptive activity of two new NO-releasing derivatives of the NSAID S-ketoprofen in rats. | |
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MedLine Citation:
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PMID: 15451773 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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1 Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) enzymes inducing analgesic, anti-inflammatory and antipyretic actions. They are not devoid of severe side effects and so, the search for new compounds with similar or higher effectiveness and a lower incidence of undesired actions is important. Nitric oxide (NO)-releasing NSAIDs resulted from this search. 2 We have compared the antinociceptive effectiveness of cumulative doses of two new NO-releasing derivatives of S-ketoprofen, HCT-2037 and HCT-2040, using the recording of spinal cord nociceptive reflexes in anesthetized and awake rats and after intravenous and oral administration. 3 S-ketoprofen and HCT-2040 were equieffective in reducing responses to noxious mechanical stimulation after i.v. administration in anesthetized animals (ID50s: 1.3+/-0.1 and 1.6+/-0.2 micromol kg(-1) respectively), but did not modify wind-up. HCT-2037 was two-fold more potent (ID50 of 0.75+/-0.1 micromol kg(-1)) in responses to mechanical stimuli and very effective in reducing wind-up (63+/-17% of control; P<0.01; MED: 0.4 micromol kg(-1)), indicating a greater activity than the parent compound. 4 In awake animals with inflammation, HCT-2037 p.o. fully inhibited mechanical allodynia, 91+/-12% reduction, and hyperalgesia, 94+/-8% reduction. Equivalent doses of S-ketoprofen only partially reduced either allodynia (50+/-11%) or hyperalgesia (40+/-4%). The effect on responses to noxious thermal stimulation was similar for the two compounds. 5 We conclude that the molecular changes made in the structure of S-ketoprofen including an NO moiety in its structure, improve the antinociceptive profile of the compound opening new perspectives in a safer use of NSAIDs as analgesic drugs. |
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Authors:
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Gema Gaitan; F Javier Ahuir; Piero Del Soldato; Juan F Herrero |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2004-09-27 |
Journal Detail:
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Title: British journal of pharmacology Volume: 143 ISSN: 0007-1188 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2004 Nov |
Date Detail:
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Created Date: 2004-10-29 Completed Date: 2005-04-28 Revised Date: 2013-06-09 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 533-40 Citation Subset: IM |
Affiliation:
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Departamento de Fisiología, Facultad de Medicina, Universidad de Alcalá, Madrid, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analgesics* Anesthesia Animals Anti-Inflammatory Agents, Non-Steroidal / pharmacology* Behavior, Animal / drug effects Blood Pressure / drug effects Carrageenan Dose-Response Relationship, Drug Edema / chemically induced, prevention & control Electric Stimulation Ketoprofen / analogs & derivatives*, pharmacology* Male Motor Neurons / drug effects Muscle, Skeletal / drug effects, innervation Nitric Oxide / metabolism* Pain Measurement / drug effects Physical Stimulation Rats Rats, Wistar Reflex / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Analgesics; 0/Anti-Inflammatory Agents, Non-Steroidal; 10102-43-9/Nitric Oxide; 22071-15-4/Ketoprofen; 9000-07-1/Carrageenan |
| Comments/Corrections | |
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