Markedly reduced toxicity of a hydrogen sulphide-releasing derivative of naproxen (ATB-346).

British Journal of Pharmacology
John L WallaceG Cirino

Abstract

Hydrogen sulphide is an important mediator of gastric mucosal defence. The use of non-steroidal anti-inflammatory drugs continues to be limited by their toxicity, particularly in the upper gastrointestinal tract. We evaluated the gastrointestinal safety and anti-inflammatory efficacy of a novel hydrogen sulphide-releasing derivative of naproxen, ATB-346 [2-(6-methoxy-napthalen-2-yl)-propionic acid 4-thiocarbamoyl-phenyl ester]. The ability of ATB-346 versus naproxen to cause gastric damage was evaluated in healthy rats and in rats with compromised gastric mucosal defence. Effects on the small intestine and on the healing of ulcers were also assessed. The ability of ATB-346 to inhibit cyclooxygenase-1 and 2 and to reduce inflammation in vivo was also evaluated. ATB-346 suppressed gastric prostaglandin E(2) synthesis as effectively as naproxen, but produced negligible damage in the stomach and intestine. In situations in which the gastric mucosa was rendered significantly more susceptible to naproxen-induced damage (e.g. ablation of sensory afferent nerves, inhibition of endogenous nitric oxide or hydrogen sulphide synthesis, co-administration with aspirin, antagonism of K(IR)6.x channels), ATB-346 did not cause significant damag...Continue Reading

References

Mar 1, 1971·The American Journal of Digestive Diseases·S OkabeC J Pfeiffer
Apr 12, 1994·Proceedings of the National Academy of Sciences of the United States of America·J L MasferrerK Seibert
Jan 1, 1993·Canadian Journal of Physiology and Pharmacology·J L Wallace
Mar 26, 1999·Gastroenterology·S J BrandM B Grisham
Dec 10, 1999·British Journal of Pharmacology·N MaricicB M Peskar
Sep 17, 2002·Proceedings of the National Academy of Sciences of the United States of America·Li MaJohn L Wallace
Nov 1, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Rui Wang
Feb 18, 2003·Fundamental & Clinical Pharmacology·John L Wallace, Piero Del Soldato
Sep 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·Stefano FiorucciAntonio Morelli
Sep 30, 2005·The Journal of Pharmacology and Experimental Therapeutics·Eleonora DistruttiStefano Fiorucci
Jan 6, 2006·The Journal of Clinical Investigation·Tilo GrosserGarret A FitzGerald
Feb 18, 2006·Nature Reviews. Drug Discovery·Jane A Mitchell, Timothy D Warner
Jul 13, 2006·Gastroenterology·Stefano FiorucciJohn L Wallace
Aug 17, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Renata C O ZanardoJohn L Wallace
Nov 15, 2006·Gastroenterology·Rudolf SchichoMichael Schemann
Jan 30, 2007·Current Medical Research and Opinion·Angel Lanas, James Scheiman
Feb 13, 2007·Free Radical Biology & Medicine·Ling LiPhilip Keith Moore
Jul 20, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·John L WallaceGary R Martin
Sep 22, 2007·Trends in Pharmacological Sciences·John L Wallace
May 2, 2008·British Journal of Pharmacology·S P H AlexanderJ A Peters
Jun 3, 2008·Journal of Neurochemistry·David R LindenJoseph H Szurszewski
Jun 28, 2008·American Journal of Physiology. Gastrointestinal and Liver Physiology·Genevieve K DudarJohn L Wallace
Feb 24, 2009·Trends in Pharmacological Sciences·John L WallaceManlio Bolla
Apr 21, 2009·Gastroenterology·John L WallaceGary R Martin
May 16, 2009·Clinics in Liver Disease·Paul Martin

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Citations

Feb 9, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·M Scott Vandiver, Solomon H Snyder
Jul 16, 2010·Journal of Cardiovascular Translational Research·Benjamin L Predmore, David J Lefer
Oct 25, 2011·Antioxidants & Redox Signaling·John L WallaceMarcelo N Muscara
Apr 10, 2013·World Journal of Gastroenterology : WJG·John L Wallace
Dec 10, 2013·European Journal of Pharmacology·Barbara RengaStefano Fiorucci
Apr 16, 2013·Antioxidants & Redox Signaling·Khosrow Kashfi
Apr 16, 2013·Antioxidants & Redox Signaling·David R Linden
Feb 12, 2014·Proceedings of the National Academy of Sciences of the United States of America·Adrienne L KingDavid J Lefer
Apr 22, 2014·Chemico-biological Interactions·Beata Olas
Jun 16, 2014·Current Opinion in Pharmacology·Rory W BlacklerJohn L Wallace
Jan 19, 2011·Current Rheumatology Reports·Trinidad Montero-MelendezMauro Perretti
Mar 20, 2012·Digestive Diseases and Sciences·John L Wallace
Jun 15, 2013·Digestive Diseases and Sciences·Hiroshi SatohKoji Takeuchi
May 23, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Marcin MagierowskiTomasz Brzozowski
Sep 26, 2015·Journal of Enzyme Inhibition and Medicinal Chemistry·Nasir UllahCarlos A Velázquez-Martínez
Nov 26, 2015·Expert Opinion on Drug Discovery·Vincenzo CalderoneMaria C Breschi
Jan 18, 2016·European Journal of Medicinal Chemistry·Marco MiglioreRita Scarpelli
Jan 12, 2016·Journal of Medicinal Chemistry·Daniel PlanoArun Kumar Sharma
Feb 24, 2016·Journal of Enzyme Inhibition and Medicinal Chemistry·Heng SongGuizhen Ao
Oct 30, 2012·Biochemical Pharmacology·Khosrow Kashfi, Kenneth R Olson
Sep 29, 2011·Gastrointestinal Endoscopy Clinics of North America·Iris Lee, Byron Cryer
Jul 19, 2011·Pharmacology & Therapeutics·Nicola J Truss, Timothy D Warner
Oct 19, 2010·Gastroenterology Clinics of North America·John L Wallace, Jose G P Ferraz
Sep 1, 2015·Current Opinion in Pharmacology·Oksana Sulaieva, John L Wallace
Aug 26, 2015·Current Treatment Options in Gastroenterology·John L WallaceOksana Sulaieva
Sep 2, 2015·Nitric Oxide : Biology and Chemistry·Serap GurWayne J G Hellstrom
Oct 13, 2012·Medicinal Research Reviews·Alma MartelliVincenzo Calderone
Oct 17, 2014·Medicinal Research Reviews·Sharad Kumar Suthar, Manu Sharma
Aug 6, 2014·British Journal of Pharmacology·Eelke M BosHenri G D Leuvenink
Oct 10, 2014·British Journal of Pharmacology·Rory W BlacklerJohn L Wallace
Jan 28, 2014·Chemical Biology & Drug Design·Tamanna Narsinghani, Rajesh Sharma
Apr 17, 2016·Translational Research : the Journal of Laboratory and Clinical Medicine·Devendra Pratap SinghManish Nivsarkar
Jan 1, 2015·Microorganisms·Sudha B Singh, Henry C Lin
Dec 19, 2014·Journal of Gastroenterology and Hepatology·Sandor Szabo
Aug 19, 2014·Circulation Journal : Official Journal of the Japanese Circulation Society·Larry A Barr, John W Calvert

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