{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:51:13Z","timestamp":1790193073000,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"3-4","license":[{"start":{"date-parts":[[2007,1,2]],"date-time":"2007-01-02T00:00:00Z","timestamp":1167696000000},"content-version":"vor","delay-in-days":123,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiovascular Drug Reviews"],"published-print":{"date-parts":[[2006,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Nitric oxide (NO), is known to exert vasodilatory, bronchodilatory, and antiplatelet effects, and quantitative or functional NO deficiency has been implicated in various cardio\u2010vascular and airway diseases. NO donors, which are drugs capable of releasing NO either spontaneously or tissue\u2010dependently, represent a way of increasing NO. Here, we review our current understanding of the NO donor, GEA 3175, 1,2,3,4\u2010oxatriazolium, 3\u2010(3\u2010chloro\u20102\u2010methylphenyl)\u20105\u2010[[(methylphenyl)sulphonyl]amino], hydroxide inner salt. GEA 3175 is a mesoionic 3\u2010aryl substituted oxatriazole\u20105\u2010imine derivative, which is a potent, stable, slow releasing NO donor with important actions in various organ systems. In isolated guinea pig trachea, rat bronchi and bovine and human small bronchioles, GEA 3175 induces potent, long\u2010lasting relaxation.<jats:italic>In vivo<\/jats:italic>, in sensitized guinea pigs, GEA 3175 protects against antigen\u2010induced bronchoconstriction. GEA 3175 also exerts potent vasodilatory properties. In isolated human pulmonary arteries, GEA 3175 induces relaxation which is long\u2010lasting and more potent than in airways. In isolated systemic arteries, GEA 3175 is also a potent vasodilator. By intravenous infusion GEA 3175 reduces blood pressure similarly to nitroglycerin. Vascular and bronchiolar relaxations were shown to be mediated via NO dependent pathways. GEA 3175 is also a potent anti\u2010inflammatory agent. Functions of polymorphnuclear cells (PMNs) such as leucotriene B<jats:sub>4<\/jats:sub>(LTB<jats:sub>4<\/jats:sub>) \u2014 synhesis, chemotaxis and superoxide (O<jats:sup>\u2212<\/jats:sup><jats:sub>2<\/jats:sub>) production are inhibited by GEA 3175. GEA3175 also inhibits upregulation of E\u2010selectin in human umbilical vein endothelial cells (HUVECs) and hence adhesion of neutrophils. Another action of GEA 3175 on the endothelium is inhibition of prostacyclin release. Finally, GEA 3175 has been demonstrated to be an antiplatelet agent. Thrombin\u2010induced platelet aggregation was inhibited by GEA 3175 in a cyclic GMP\u2010 and vasodilator\u2010stimulated phosphoprotein (VASP)\u2010phosphorylation\u2010dependent manner. Thus, GEA 3175 has been demonstrated to exert bronchodilatory, pulmonary vasodilatory, antiplatelet as well as anti\u2010inflammatory actions. Given these actions GEA 3175 may represent a potentially useful drug. The exact mechanism whereby GEA 3175 releases NO is, however, still unknown. In addition, most of the studies so far have been performed in isolated tissue preparations. Clearly, further<jats:italic>in vivo<\/jats:italic>studies involving animal models are required to clarify safety issues and whether GEA 3175 can be used in the treatment of pulmonary hypertension and\/or airway diseases.<\/jats:p>","DOI":"10.1111\/j.1527-3466.2006.00247.x","type":"journal-article","created":{"date-parts":[[2007,1,2]],"date-time":"2007-01-02T17:57:03Z","timestamp":1167760623000},"page":"247-260","source":"Crossref","is-referenced-by-count":16,"title":["Potential Protective Properties of a Stable, Slow\u2010releasing Nitric Oxide Donor, GEA 3175, in the Lung"],"prefix":"10.1111","volume":"24","author":[{"given":"Britt Elmedal","family":"Laursen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgaras","family":"Stankevicius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Pilegaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Mulvany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Simonsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,1,2]]},"reference":[{"key":"e_1_2_1_2_2","first-page":"195","article-title":"Effects of NO\u2010donors, SIN\u20101 and GEA 3175 on prostacyclin and cGMP synthesis in cultured rat endothelial cells","volume":"45","author":"Alanko J","year":"1995","journal-title":"Agents Actions Suppl"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2005.05.019"},{"issue":"3","key":"e_1_2_1_4_2","first-page":"1238","article-title":"Characterization of bronchodilator effects and fate of S\u2010nitrosothiols in the isolated perfused and ventilated guinea pig lung","volume":"272","author":"Bannenberg G","year":"1995","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.158.supplement_2.13tac800"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199602013340504"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(91)90626-2"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb16043.x"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.16.4.9115747"},{"issue":"6","key":"e_1_2_1_10_2","first-page":"553","article-title":"Pharmacology of mesoionic oxatriazole derivatives in blood, cardiovascular and respiratory systems","volume":"46","author":"Corell T","year":"1994","journal-title":"PolJ Pharmacol"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115877"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705580"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2005.04.017"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2005.05.004"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.149.2.7508323"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15654.x"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/139.5.1192"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701684"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.94.07040698"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(98)00009-0"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra040291"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1513\/pats.200402-009MS"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(97)00158-1"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.153.1.8542105"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15204.x"},{"issue":"6","key":"e_1_2_1_26_2","first-page":"541","article-title":"Mesoionic oxatriazole derivatives \u2013 a new group of NO\u2010donors","volume":"46","author":"Karup G","year":"1994","journal-title":"Pol J Pharmacol"},{"key":"e_1_2_1_27_2","unstructured":"KarupGL PreitscakHF CorellT et al.WO Patent 92\/13847.1992."},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704876"},{"key":"e_1_2_1_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-003-0024-7"},{"issue":"1","key":"e_1_2_1_30_2","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0022-3565(24)37577-9","article-title":"Nitric oxide\u2010releasing oxatriazole derivatives inhibit human lymphocyte proliferation by a cyclic GMP\u2010independent mechanism","volume":"286","author":"Kosonen O","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_1_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(99)00581-6"},{"key":"e_1_2_1_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702042"},{"key":"e_1_2_1_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(00)00141-2"},{"key":"e_1_2_1_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(97)01266-1"},{"key":"e_1_2_1_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2005.01542.x"},{"key":"e_1_2_1_36_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.50.35318"},{"key":"e_1_2_1_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.92.6.1539"},{"key":"e_1_2_1_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.96.2.689"},{"key":"e_1_2_1_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1993.tb13653.x"},{"key":"e_1_2_1_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.1991.tb01383.x"},{"issue":"2","key":"e_1_2_1_41_2","first-page":"109","article-title":"Nitric oxide: Physiology, pathophysiology, and pharmacology","volume":"43","author":"Moncada S","year":"1991","journal-title":"Pharmacol Rev"},{"issue":"6","key":"e_1_2_1_42_2","first-page":"1171","article-title":"Mechanics of airway narrowing","volume":"133","author":"Moreno RH","year":"1986","journal-title":"Am Rev Respir Dis"},{"key":"e_1_2_1_43_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.43.100901.140226"},{"key":"e_1_2_1_44_2","doi-asserted-by":"publisher","DOI":"10.1006\/pupt.2000.0262"},{"key":"e_1_2_1_45_2","first-page":"207","article-title":"Effect of nitric oxide donors on rat bronchial muscle in vitro","volume":"45","author":"Paakkari I","year":"1995","journal-title":"Agents Actions Suppl"},{"key":"e_1_2_1_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)91481-4"},{"key":"e_1_2_1_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2005.12.069"},{"key":"e_1_2_1_48_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.152.4.7551393"},{"key":"e_1_2_1_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-827X(99)00031-2"},{"key":"e_1_2_1_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704076"},{"key":"e_1_2_1_51_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-445X.1999.01887.x"},{"key":"e_1_2_1_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2004.06.002"},{"key":"e_1_2_1_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704778"},{"key":"e_1_2_1_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705909"},{"key":"e_1_2_1_55_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp020603"},{"issue":"5","key":"e_1_2_1_56_2","first-page":"260","article-title":"Adenosine 5\u2032\u2010diphosphate\u2010induced platelet aggregation in uremia shows resistance to inhibition by the novel nitric oxide donor GEA 3175 but not by S\u2010nitroso\u2010N\u2010acetylpenicillamine","volume":"28","author":"Whiss PA","year":"1998","journal-title":"Haemostasis"}],"container-title":["Cardiovascular Drug Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1527-3466.2006.00247.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1527-3466.2006.00247.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,12]],"date-time":"2025-01-12T19:19:28Z","timestamp":1736709568000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1527-3466.2006.00247.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,9]]},"references-count":55,"journal-issue":{"issue":"3-4","published-print":{"date-parts":[[2006,9]]}},"alternative-id":["10.1111\/j.1527-3466.2006.00247.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1527-3466.2006.00247.x","archive":["Portico"],"relation":{},"ISSN":["0897-5957","1527-3466"],"issn-type":[{"value":"0897-5957","type":"print"},{"value":"1527-3466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,9]]}}}