A novel class of 5-HT2A receptor antagonists: aryl aminoguanidines
Local delivery of serotonin (5-HT) produces a rapid edematous response in soft tissues via increased fluid extravasation which is prevented by 5-HT2 antagonists such as ketanserin or mianserin. Here we report the effects of a new class of aminoguanidine 5-HT2 antagonists, with relative selectivity f...
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| Veröffentlicht in: | Life sciences (1973) 1996-09, Vol.59 (15), p.1259-1268 |
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| container_end_page | 1268 |
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| container_title | Life sciences (1973) |
| container_volume | 59 |
| creator | Bryant, H U Nelson, D L Button, D Cole, H W Baez, M B Lucaites, V L Wainscott, D B Whitesitt, C Reel, J Simon, R Koppel, G A |
| description | Local delivery of serotonin (5-HT) produces a rapid edematous response in soft tissues via increased fluid extravasation which is prevented by 5-HT2 antagonists such as ketanserin or mianserin. Here we report the effects of a new class of aminoguanidine 5-HT2 antagonists, with relative selectivity for 5-HT2A receptors which are potent inhibitors of 5-HT-induced paw edema in the rat. Radioligand binding studies with 125I DOI on human 5-HT2A and 5-HT2C receptors and with 3H-5-HT on human 5-HT2B receptors demonstrated that, LY314228, and LY320954 displayed some selectivity for the 5-HT2A receptor. When compared to binding at other 5-HT2 receptor subtypes, LY314228 had an 18.6-fold greater affinity for the 5-HT2A site over the 5-HT2B site, and 2.6 fold greater at the 5-HT2C site. LY320954 displayed similar preference for 5-HT2A sites. Both compounds also inhibited 5-HT-induced paw swelling in rats, with ED50's of 6.4 and 4.8 mg/kg (for LY314228 and LY320954, respectively). These studies offer evidence for a novel class of pharmacophores for the 5-HT2 receptor family which show greater relative affinities for the 5-HT2A receptor subclass. |
| doi_str_mv | 10.1016/0024-3205(96)00449-3 |
| format | Article |
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Here we report the effects of a new class of aminoguanidine 5-HT2 antagonists, with relative selectivity for 5-HT2A receptors which are potent inhibitors of 5-HT-induced paw edema in the rat. Radioligand binding studies with 125I DOI on human 5-HT2A and 5-HT2C receptors and with 3H-5-HT on human 5-HT2B receptors demonstrated that, LY314228, and LY320954 displayed some selectivity for the 5-HT2A receptor. When compared to binding at other 5-HT2 receptor subtypes, LY314228 had an 18.6-fold greater affinity for the 5-HT2A site over the 5-HT2B site, and 2.6 fold greater at the 5-HT2C site. LY320954 displayed similar preference for 5-HT2A sites. Both compounds also inhibited 5-HT-induced paw swelling in rats, with ED50's of 6.4 and 4.8 mg/kg (for LY314228 and LY320954, respectively). These studies offer evidence for a novel class of pharmacophores for the 5-HT2 receptor family which show greater relative affinities for the 5-HT2A receptor subclass.</description><identifier>ISSN: 0024-3205</identifier><identifier>DOI: 10.1016/0024-3205(96)00449-3</identifier><identifier>PMID: 8845011</identifier><language>eng</language><publisher>Netherlands</publisher><subject>Animals ; Cell Line, Transformed ; Cell Membrane - metabolism ; Cricetinae ; Edema - chemically induced ; Female ; Guanidines - chemistry ; Guanidines - metabolism ; Guanidines - pharmacology ; Humans ; Mesocricetus ; Molecular Structure ; Ovariectomy ; Rats ; Rats, Sprague-Dawley ; Receptors, Serotonin - drug effects ; Receptors, Serotonin - metabolism ; Serotonin - metabolism ; Serotonin Antagonists - pharmacology</subject><ispartof>Life sciences (1973), 1996-09, Vol.59 (15), p.1259-1268</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c300t-1c9c2e8f72a5cda340365b50a34eacda08f63c05587acbe03edcaba79db7018e3</citedby><cites>FETCH-LOGICAL-c300t-1c9c2e8f72a5cda340365b50a34eacda08f63c05587acbe03edcaba79db7018e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8845011$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bryant, H U</creatorcontrib><creatorcontrib>Nelson, D L</creatorcontrib><creatorcontrib>Button, D</creatorcontrib><creatorcontrib>Cole, H W</creatorcontrib><creatorcontrib>Baez, M B</creatorcontrib><creatorcontrib>Lucaites, V L</creatorcontrib><creatorcontrib>Wainscott, D B</creatorcontrib><creatorcontrib>Whitesitt, C</creatorcontrib><creatorcontrib>Reel, J</creatorcontrib><creatorcontrib>Simon, R</creatorcontrib><creatorcontrib>Koppel, G A</creatorcontrib><title>A novel class of 5-HT2A receptor antagonists: aryl aminoguanidines</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>Local delivery of serotonin (5-HT) produces a rapid edematous response in soft tissues via increased fluid extravasation which is prevented by 5-HT2 antagonists such as ketanserin or mianserin. Here we report the effects of a new class of aminoguanidine 5-HT2 antagonists, with relative selectivity for 5-HT2A receptors which are potent inhibitors of 5-HT-induced paw edema in the rat. Radioligand binding studies with 125I DOI on human 5-HT2A and 5-HT2C receptors and with 3H-5-HT on human 5-HT2B receptors demonstrated that, LY314228, and LY320954 displayed some selectivity for the 5-HT2A receptor. When compared to binding at other 5-HT2 receptor subtypes, LY314228 had an 18.6-fold greater affinity for the 5-HT2A site over the 5-HT2B site, and 2.6 fold greater at the 5-HT2C site. LY320954 displayed similar preference for 5-HT2A sites. Both compounds also inhibited 5-HT-induced paw swelling in rats, with ED50's of 6.4 and 4.8 mg/kg (for LY314228 and LY320954, respectively). These studies offer evidence for a novel class of pharmacophores for the 5-HT2 receptor family which show greater relative affinities for the 5-HT2A receptor subclass.</description><subject>Animals</subject><subject>Cell Line, Transformed</subject><subject>Cell Membrane - metabolism</subject><subject>Cricetinae</subject><subject>Edema - chemically induced</subject><subject>Female</subject><subject>Guanidines - chemistry</subject><subject>Guanidines - metabolism</subject><subject>Guanidines - pharmacology</subject><subject>Humans</subject><subject>Mesocricetus</subject><subject>Molecular Structure</subject><subject>Ovariectomy</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptors, Serotonin - drug effects</subject><subject>Receptors, Serotonin - metabolism</subject><subject>Serotonin - metabolism</subject><subject>Serotonin Antagonists - pharmacology</subject><issn>0024-3205</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kMFOwzAQRH0AlVL4A5B8QnAIrGM7ibmVCihSJS7lbDnOpgpK7BInSPw9jlr1tLujmdHqEXLD4JEBy54AUpHwFOS9yh4AhFAJPyPzk3xBLkP4BgApcz4js6IQEhibk5cldf4XW2pbEwL1NZXJepsuaY8W94PvqXGD2XnXhCE8U9P_tdR0jfO70bimahyGK3Jemzbg9XEuyNfb63a1Tjaf7x-r5SaxHGBImFU2xaLOUyNtZbgAnslSQtzQRAGKOuM2PljkxpYIHCtrSpOrqsyBFcgX5O7Qu-_9z4hh0F0TLLatcejHoPNCgBKZikZxMNreh9Bjrfd908XXNQM94dITFz1x0Wo6Ii7NY-z22D-WHVan0JEV_wcm4mdB</recordid><startdate>199609</startdate><enddate>199609</enddate><creator>Bryant, H U</creator><creator>Nelson, D L</creator><creator>Button, D</creator><creator>Cole, H W</creator><creator>Baez, M B</creator><creator>Lucaites, V L</creator><creator>Wainscott, D B</creator><creator>Whitesitt, C</creator><creator>Reel, J</creator><creator>Simon, R</creator><creator>Koppel, G A</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>199609</creationdate><title>A novel class of 5-HT2A receptor antagonists: aryl aminoguanidines</title><author>Bryant, H U ; Nelson, D L ; Button, D ; Cole, H W ; Baez, M B ; Lucaites, V L ; Wainscott, D B ; Whitesitt, C ; Reel, J ; Simon, R ; Koppel, G A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c300t-1c9c2e8f72a5cda340365b50a34eacda08f63c05587acbe03edcaba79db7018e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Animals</topic><topic>Cell Line, Transformed</topic><topic>Cell Membrane - metabolism</topic><topic>Cricetinae</topic><topic>Edema - chemically induced</topic><topic>Female</topic><topic>Guanidines - chemistry</topic><topic>Guanidines - metabolism</topic><topic>Guanidines - pharmacology</topic><topic>Humans</topic><topic>Mesocricetus</topic><topic>Molecular Structure</topic><topic>Ovariectomy</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptors, Serotonin - drug effects</topic><topic>Receptors, Serotonin - metabolism</topic><topic>Serotonin - metabolism</topic><topic>Serotonin Antagonists - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bryant, H U</creatorcontrib><creatorcontrib>Nelson, D L</creatorcontrib><creatorcontrib>Button, D</creatorcontrib><creatorcontrib>Cole, H W</creatorcontrib><creatorcontrib>Baez, M B</creatorcontrib><creatorcontrib>Lucaites, V L</creatorcontrib><creatorcontrib>Wainscott, D B</creatorcontrib><creatorcontrib>Whitesitt, C</creatorcontrib><creatorcontrib>Reel, J</creatorcontrib><creatorcontrib>Simon, R</creatorcontrib><creatorcontrib>Koppel, G A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bryant, H U</au><au>Nelson, D L</au><au>Button, D</au><au>Cole, H W</au><au>Baez, M B</au><au>Lucaites, V L</au><au>Wainscott, D B</au><au>Whitesitt, C</au><au>Reel, J</au><au>Simon, R</au><au>Koppel, G A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A novel class of 5-HT2A receptor antagonists: aryl aminoguanidines</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>1996-09</date><risdate>1996</risdate><volume>59</volume><issue>15</issue><spage>1259</spage><epage>1268</epage><pages>1259-1268</pages><issn>0024-3205</issn><abstract>Local delivery of serotonin (5-HT) produces a rapid edematous response in soft tissues via increased fluid extravasation which is prevented by 5-HT2 antagonists such as ketanserin or mianserin. 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| ispartof | Life sciences (1973), 1996-09, Vol.59 (15), p.1259-1268 |
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| language | eng |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Animals Cell Line, Transformed Cell Membrane - metabolism Cricetinae Edema - chemically induced Female Guanidines - chemistry Guanidines - metabolism Guanidines - pharmacology Humans Mesocricetus Molecular Structure Ovariectomy Rats Rats, Sprague-Dawley Receptors, Serotonin - drug effects Receptors, Serotonin - metabolism Serotonin - metabolism Serotonin Antagonists - pharmacology |
| title | A novel class of 5-HT2A receptor antagonists: aryl aminoguanidines |
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