{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T04:14:15Z","timestamp":1745554455593,"version":"3.40.4"},"reference-count":3,"publisher":"S. Karger AG","issue":"2","license":[{"start":{"date-parts":[[1998,1,1]],"date-time":"1998-01-01T00:00:00Z","timestamp":883612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[1998,1,1]],"date-time":"1998-01-01T00:00:00Z","timestamp":883612800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int Arch Allergy Immunol"],"published-print":{"date-parts":[[1998]]},"abstract":"<b>Background:<\/b> Histamine is a critical mediator of immediate hypersensitivity reactions. Sensory neuropeptides, such as substance P (SP), may also contribute to acute inflammatory responses. A compound which antagonizes both H<sub>1<\/sub> and NK-1 receptors, such as MDL 108,207DA, may present a significant therapeutic advantage over pure antihistamines. <b>Methods:<\/b> The binding affinity of MDL 108,207DA for H<sub>1<\/sub> and NK-1 receptors was evaluated and its potency of antagonism evaluated in vitro. The in vivo antagonism of SP- or histamine-induced microvascular leakage in guinea pig airways was examined. A role for these mediators in antigen-induced microvascular leakage in ovalbumin-sensitized guinea pig airways was examined using MDL 108,207DA as well as the NK-1-selective antagonist FK888 and the H<sub>1<\/sub>-selective antagonist pyrilamine alone or in combination. <b>Results:<\/b> The affinity of MDL 108,207DA for H<sub>1<\/sub> and NK-1 receptors is similar to that of receptor-selective antagonists. The compound inhibits both receptors in vitro and in vivo with comparable potencies for each. The efficacy of FK888 in combination with pyrilamine and MDL 108,207DA on antigen-induced microvascular leakage in sensitized guinea pig airways supports a role for both SP and histamine in early allergic responses. <b>Conclusion:<\/b> The contribution of both SP and histamine to immediate hypersensitivity reactions supports the utility of NK-1 and H<sub>1<\/sub> receptor antagonist therapy. MDL 108,207DA incorporates both activities into the same compound and, as a result, may be useful in the treatment of allergic diseases.<\/jats:p>","DOI":"10.1159\/000023898","type":"journal-article","created":{"date-parts":[[2003,4,15]],"date-time":"2003-04-15T10:10:37Z","timestamp":1050401437000},"page":"169-178","source":"Crossref","is-referenced-by-count":6,"title":["A Role for Histamine and Substance P in Immediate Allergic Responses in Guinea Pig Airways: Characterization of MDL 108,207DA, a Dual H<sub>1<\/sub> \/ NK-1 Receptor Antagonist"],"prefix":"10.1159","volume":"115","author":[{"given":"Elizabeth","family":"Kudlacz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott","family":"Shatzer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah","family":"Logan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl","family":"Olsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Knippenberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lily","family":"Hsieh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hector","family":"Esteve","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Maynard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[1998,1,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199406093302307"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1993.2662"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/0167-0115(88)90387-4"}],"container-title":["International Archives of Allergy and Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/23898","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/23898","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T04:52:27Z","timestamp":1745470347000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000023898"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998]]},"references-count":3,"journal-issue":{"issue":"2","published-online":{"date-parts":[[1998,2,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000023898","archive":["Portico"],"relation":{},"ISSN":["1018-2438","1423-0097"],"issn-type":[{"type":"print","value":"1018-2438"},{"type":"electronic","value":"1423-0097"}],"subject":[],"published":{"date-parts":[[1998]]}}}