{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T05:33:27Z","timestamp":1770960807852,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":2616,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2001,12]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Initiation of a peritoneal Arthus reaction by deposition of immune\u2010complexes results in vascular leakage, polymorphonuclear leukocyte (PMN) infiltration, and tumour necrosis factor \u03b1 (TNF\u03b1) and interleukin\u20106 (IL\u20106) production. We now demonstrate in rats that oral administration of the C5a receptor antagonist AcPhe[Orn\u2010Pro\u2010D\u2010Cyclohexylalanine\u2010Trp\u2010Arg] (AcF\u2010[OPdChaWR]; 1\u2003\u2013\u200310\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> 30\u2003min prior to immune\u2010complex deposition) inhibits these inflammatory markers in the peritoneal Arthus reaction.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Initiation of a dermal Arthus reaction resulted in a significant increase in vascular leakage, PMN infiltration, systemic production of TNF\u03b1 and pathological changes in the dermis.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Pretreatment of rats with AcF\u2010[OPdChaWR] either intravenously (1\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> 10\u2003min prior to immune\u2010complex deposition) or orally (1\u2003\u2013\u200310\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> 30\u2003min prior to immune\u2010complex deposition) significantly inhibited immune\u2010complex mediated dermal vascular leakage and systemic cytokine production. Topical pretreatment with AcF\u2010[OPdChaWR] (400\u2003\u03bcg\u2003site<jats:sup>\u22121<\/jats:sup> in 10% dimethyl sulphoxide 10\u2003min prior to immune\u2010complex deposition) also inhibited vascular leakage, as well as histopathological changes associated with a dermal Arthus reaction.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Oral administration of 3\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> AcF\u2010[OPdChaWR] resulted in the appearance of the drug in plasma within 5\u2003min, with peak blood levels \u223c0.3\u2003\u03bc<jats:sc>M<\/jats:sc> reached within 20\u2003min. The plasma elimination half\u2010life was \u223c70\u2003min. The oral activity and bioavailability of AcF\u2010[OPdChaWR], its activity when applied topically to the skin, suggest that small molecule C5a receptor antagonists may have therapeutic utility in dermal inflammatory disorders involving complement activation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This is the first demonstration for either an orally or topically active C5a receptor antagonist, and suggests that small molecule C5a antagonists may have therapeutic utility when given by multiple routes of application.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2001) <jats:bold>134<\/jats:bold>, 1778\u20131786; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0704417\">10.1038\/sj.bjp.0704417<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0704417","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T21:39:21Z","timestamp":1106948361000},"page":"1778-1786","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Inhibition of immune\u2010complex mediated dermal inflammation in rats following either oral or topical administration of a small molecule C5a receptor antagonist"],"prefix":"10.1111","volume":"134","author":[{"given":"Anna J","family":"Strachan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian A","family":"Shiels","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert C","family":"Reid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David P","family":"Fairlie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen M","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.320.7240.963"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.2.1065"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1993.tb13897.x"},{"key":"e_1_2_7_5_1","first-page":"933","article-title":"NPC 15669 inhibits the reversed passive Arthus reaction in rats by blocking neutrophil recruitment","volume":"263","author":"BURCH R.M.","year":"1992","journal-title":"J. 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