Pharmacological characterization of a novel, orally active, nonpeptide bradykinin B2 receptor antagonist, FR167344
To investigate the pathophysiological role of bradykinin and to develop a drug for inflammatory diseases, we discovered an orally active, nonpeptide bradykinin B2 receptor antagonist, FR167344, N-[N-[3-[(3-bromo-2-methylimidazo[1,2-a]pyridin-8-yl)oxymethyl]-2, 4dichlorophenyl]-N-methylaminocarbonylm...
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| Veröffentlicht in: | European journal of pharmacology 1997-08, Vol.333 (1), p.79-86 |
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| creator | INAMURA, N ASANO, M SAWADA, Y OKU, T NAKAHARA, K HATORI, C SAWAI, H HIROSUMI, J FUJIWARA, T KAYAKIRI, H SATOH, S ABE, Y INOUE, T |
| description | To investigate the pathophysiological role of bradykinin and to develop a drug for inflammatory diseases, we discovered an orally active, nonpeptide bradykinin B2 receptor antagonist, FR167344, N-[N-[3-[(3-bromo-2-methylimidazo[1,2-a]pyridin-8-yl)oxymethyl]-2, 4dichlorophenyl]-N-methylaminocarbonylmethyl]-4-(dimethyl aminocarbonyl) cinnamylamide hydrochloride. This compound competitively displaced [3H]bradykinin binding to bradykinin B2 receptors present in guinea-pig ileum membrane with an IC50 value of 6.6 X 10(-10) M. In isolated guinea-pig ileum preparations, it also antagonized bradykinin-induced contraction with a pA2 value of 9.3. In human lung fibroblast IMR-90 cells, FR167344 displaced [3H]bradykinin binding to human bradykinin B2 receptors with an IC50 value of 1.3 X 10(-8) M, but not [3H]des-Arg10-kallidin binding to human bradykinin B1 receptors. In vivo, oral administration of FR167344 inhibited bradykinin-induced bronchoconstriction in guinea pigs and the bradykinin-induced hypotensive response for 6 h in rats. These results show that FR167344 is a potent, selective, orally active and long acting bradykinin B2 receptor antagonist. |
| doi_str_mv | 10.1016/s0014-2999(97)01100-x |
| format | Article |
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This compound competitively displaced [3H]bradykinin binding to bradykinin B2 receptors present in guinea-pig ileum membrane with an IC50 value of 6.6 X 10(-10) M. In isolated guinea-pig ileum preparations, it also antagonized bradykinin-induced contraction with a pA2 value of 9.3. In human lung fibroblast IMR-90 cells, FR167344 displaced [3H]bradykinin binding to human bradykinin B2 receptors with an IC50 value of 1.3 X 10(-8) M, but not [3H]des-Arg10-kallidin binding to human bradykinin B1 receptors. In vivo, oral administration of FR167344 inhibited bradykinin-induced bronchoconstriction in guinea pigs and the bradykinin-induced hypotensive response for 6 h in rats. These results show that FR167344 is a potent, selective, orally active and long acting bradykinin B2 receptor antagonist.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/s0014-2999(97)01100-x</identifier><identifier>PMID: 9311664</identifier><identifier>CODEN: EJPHAZ</identifier><language>eng</language><publisher>Amsterdam: Elsevier</publisher><subject>Animals ; Aorta, Thoracic - drug effects ; Biological and medical sciences ; Blood Pressure - drug effects ; Bradykinin - antagonists & inhibitors ; Bradykinin - pharmacology ; Bradykinin Receptor Antagonists ; Bronchoconstriction - drug effects ; Female ; Fibroblasts ; Fundamental and applied biological sciences. Psychology ; Guinea Pigs ; Humans ; Ileum - drug effects ; In Vitro Techniques ; Inflammation ; Medical sciences ; Molecular and cellular biology ; Muscle Contraction - drug effects ; Muscle, Smooth - drug effects ; Muscle, Smooth, Vascular - drug effects ; Pharmacology. Drug treatments ; Pyridines - metabolism ; Pyridines - pharmacology ; Rabbits ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Receptor, Bradykinin B2 ; Receptors, Bradykinin - metabolism ; Respiratory system</subject><ispartof>European journal of pharmacology, 1997-08, Vol.333 (1), p.79-86</ispartof><rights>1997 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c314t-911ca1cca180dfb4b1234cc42daabcdf0cc69ca23d630638767e42cd8ef112f13</citedby><cites>FETCH-LOGICAL-c314t-911ca1cca180dfb4b1234cc42daabcdf0cc69ca23d630638767e42cd8ef112f13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2795513$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9311664$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>INAMURA, N</creatorcontrib><creatorcontrib>ASANO, M</creatorcontrib><creatorcontrib>SAWADA, Y</creatorcontrib><creatorcontrib>OKU, T</creatorcontrib><creatorcontrib>NAKAHARA, K</creatorcontrib><creatorcontrib>HATORI, C</creatorcontrib><creatorcontrib>SAWAI, H</creatorcontrib><creatorcontrib>HIROSUMI, J</creatorcontrib><creatorcontrib>FUJIWARA, T</creatorcontrib><creatorcontrib>KAYAKIRI, H</creatorcontrib><creatorcontrib>SATOH, S</creatorcontrib><creatorcontrib>ABE, Y</creatorcontrib><creatorcontrib>INOUE, T</creatorcontrib><title>Pharmacological characterization of a novel, orally active, nonpeptide bradykinin B2 receptor antagonist, FR167344</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>To investigate the pathophysiological role of bradykinin and to develop a drug for inflammatory diseases, we discovered an orally active, nonpeptide bradykinin B2 receptor antagonist, FR167344, N-[N-[3-[(3-bromo-2-methylimidazo[1,2-a]pyridin-8-yl)oxymethyl]-2, 4dichlorophenyl]-N-methylaminocarbonylmethyl]-4-(dimethyl aminocarbonyl) cinnamylamide hydrochloride. This compound competitively displaced [3H]bradykinin binding to bradykinin B2 receptors present in guinea-pig ileum membrane with an IC50 value of 6.6 X 10(-10) M. In isolated guinea-pig ileum preparations, it also antagonized bradykinin-induced contraction with a pA2 value of 9.3. In human lung fibroblast IMR-90 cells, FR167344 displaced [3H]bradykinin binding to human bradykinin B2 receptors with an IC50 value of 1.3 X 10(-8) M, but not [3H]des-Arg10-kallidin binding to human bradykinin B1 receptors. In vivo, oral administration of FR167344 inhibited bradykinin-induced bronchoconstriction in guinea pigs and the bradykinin-induced hypotensive response for 6 h in rats. These results show that FR167344 is a potent, selective, orally active and long acting bradykinin B2 receptor antagonist.</description><subject>Animals</subject><subject>Aorta, Thoracic - drug effects</subject><subject>Biological and medical sciences</subject><subject>Blood Pressure - drug effects</subject><subject>Bradykinin - antagonists & inhibitors</subject><subject>Bradykinin - pharmacology</subject><subject>Bradykinin Receptor Antagonists</subject><subject>Bronchoconstriction - drug effects</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Guinea Pigs</subject><subject>Humans</subject><subject>Ileum - drug effects</subject><subject>In Vitro Techniques</subject><subject>Inflammation</subject><subject>Medical sciences</subject><subject>Molecular and cellular biology</subject><subject>Muscle Contraction - drug effects</subject><subject>Muscle, Smooth - drug effects</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Pharmacology. Drug treatments</subject><subject>Pyridines - metabolism</subject><subject>Pyridines - pharmacology</subject><subject>Rabbits</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Rats, Wistar</subject><subject>Receptor, Bradykinin B2</subject><subject>Receptors, Bradykinin - metabolism</subject><subject>Respiratory system</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kN2KFDEQhYMo67j6CAu5EFGY1lSS7nQudXFVWFD8Ae9CdXV6jfYkY9KzOD69GXeYi6Koc05VwcfYBYiXIKB7VYQA3Uhr7XNrXggAIZo_99gKemMbYUDeZ6tT5CF7VMpPIURrZXvGzqwC6Dq9YvnTD8wbpDSnm0A4c6oz0uJz-ItLSJGniSOP6dbPa54yzvOeVz_c-nVV49ZvlzB6PmQc979CDJG_kTx7qnrKHOOCNymGsqz51WfojNL6MXsw4Vz8k2M_Z9-u3n69fN9cf3z34fL1dUMK9NJYAEKgWr0Yp0EPIJUm0nJEHGicBFFnCaUaOyU61ZvOeC1p7P0EICdQ5-zZ3d1tTr93vixuEwr5ecbo0644UyGoXpsabO-ClFMp2U9um8MG896BcAfW7ssBpDuAdNa4_6zd97p3cXywGzZ-PG0d4Vb_6dHHUtFOGSOFcopJY9sWlPoHtV6ISg</recordid><startdate>19970820</startdate><enddate>19970820</enddate><creator>INAMURA, N</creator><creator>ASANO, M</creator><creator>SAWADA, Y</creator><creator>OKU, T</creator><creator>NAKAHARA, K</creator><creator>HATORI, C</creator><creator>SAWAI, H</creator><creator>HIROSUMI, J</creator><creator>FUJIWARA, T</creator><creator>KAYAKIRI, H</creator><creator>SATOH, S</creator><creator>ABE, Y</creator><creator>INOUE, T</creator><general>Elsevier</general><scope>IQODW</scope><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>19970820</creationdate><title>Pharmacological characterization of a novel, orally active, nonpeptide bradykinin B2 receptor antagonist, FR167344</title><author>INAMURA, N ; ASANO, M ; SAWADA, Y ; OKU, T ; NAKAHARA, K ; HATORI, C ; SAWAI, H ; HIROSUMI, J ; FUJIWARA, T ; KAYAKIRI, H ; SATOH, S ; ABE, Y ; INOUE, T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c314t-911ca1cca180dfb4b1234cc42daabcdf0cc69ca23d630638767e42cd8ef112f13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Animals</topic><topic>Aorta, Thoracic - drug effects</topic><topic>Biological and medical sciences</topic><topic>Blood Pressure - drug effects</topic><topic>Bradykinin - antagonists & inhibitors</topic><topic>Bradykinin - pharmacology</topic><topic>Bradykinin Receptor Antagonists</topic><topic>Bronchoconstriction - drug effects</topic><topic>Female</topic><topic>Fibroblasts</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Guinea Pigs</topic><topic>Humans</topic><topic>Ileum - drug effects</topic><topic>In Vitro Techniques</topic><topic>Inflammation</topic><topic>Medical sciences</topic><topic>Molecular and cellular biology</topic><topic>Muscle Contraction - drug effects</topic><topic>Muscle, Smooth - drug effects</topic><topic>Muscle, Smooth, Vascular - drug effects</topic><topic>Pharmacology. Drug treatments</topic><topic>Pyridines - metabolism</topic><topic>Pyridines - pharmacology</topic><topic>Rabbits</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Rats, Wistar</topic><topic>Receptor, Bradykinin B2</topic><topic>Receptors, Bradykinin - metabolism</topic><topic>Respiratory system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>INAMURA, N</creatorcontrib><creatorcontrib>ASANO, M</creatorcontrib><creatorcontrib>SAWADA, Y</creatorcontrib><creatorcontrib>OKU, T</creatorcontrib><creatorcontrib>NAKAHARA, K</creatorcontrib><creatorcontrib>HATORI, C</creatorcontrib><creatorcontrib>SAWAI, H</creatorcontrib><creatorcontrib>HIROSUMI, J</creatorcontrib><creatorcontrib>FUJIWARA, T</creatorcontrib><creatorcontrib>KAYAKIRI, H</creatorcontrib><creatorcontrib>SATOH, S</creatorcontrib><creatorcontrib>ABE, Y</creatorcontrib><creatorcontrib>INOUE, T</creatorcontrib><collection>Pascal-Francis</collection><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>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>INAMURA, N</au><au>ASANO, M</au><au>SAWADA, Y</au><au>OKU, T</au><au>NAKAHARA, K</au><au>HATORI, C</au><au>SAWAI, H</au><au>HIROSUMI, J</au><au>FUJIWARA, T</au><au>KAYAKIRI, H</au><au>SATOH, S</au><au>ABE, Y</au><au>INOUE, T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacological characterization of a novel, orally active, nonpeptide bradykinin B2 receptor antagonist, FR167344</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>1997-08-20</date><risdate>1997</risdate><volume>333</volume><issue>1</issue><spage>79</spage><epage>86</epage><pages>79-86</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>To investigate the pathophysiological role of bradykinin and to develop a drug for inflammatory diseases, we discovered an orally active, nonpeptide bradykinin B2 receptor antagonist, FR167344, N-[N-[3-[(3-bromo-2-methylimidazo[1,2-a]pyridin-8-yl)oxymethyl]-2, 4dichlorophenyl]-N-methylaminocarbonylmethyl]-4-(dimethyl aminocarbonyl) cinnamylamide hydrochloride. This compound competitively displaced [3H]bradykinin binding to bradykinin B2 receptors present in guinea-pig ileum membrane with an IC50 value of 6.6 X 10(-10) M. In isolated guinea-pig ileum preparations, it also antagonized bradykinin-induced contraction with a pA2 value of 9.3. In human lung fibroblast IMR-90 cells, FR167344 displaced [3H]bradykinin binding to human bradykinin B2 receptors with an IC50 value of 1.3 X 10(-8) M, but not [3H]des-Arg10-kallidin binding to human bradykinin B1 receptors. In vivo, oral administration of FR167344 inhibited bradykinin-induced bronchoconstriction in guinea pigs and the bradykinin-induced hypotensive response for 6 h in rats. These results show that FR167344 is a potent, selective, orally active and long acting bradykinin B2 receptor antagonist.</abstract><cop>Amsterdam</cop><pub>Elsevier</pub><pmid>9311664</pmid><doi>10.1016/s0014-2999(97)01100-x</doi><tpages>8</tpages></addata></record> |
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| ispartof | European journal of pharmacology, 1997-08, Vol.333 (1), p.79-86 |
| issn | 0014-2999 1879-0712 |
| language | eng |
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| subjects | Animals Aorta, Thoracic - drug effects Biological and medical sciences Blood Pressure - drug effects Bradykinin - antagonists & inhibitors Bradykinin - pharmacology Bradykinin Receptor Antagonists Bronchoconstriction - drug effects Female Fibroblasts Fundamental and applied biological sciences. Psychology Guinea Pigs Humans Ileum - drug effects In Vitro Techniques Inflammation Medical sciences Molecular and cellular biology Muscle Contraction - drug effects Muscle, Smooth - drug effects Muscle, Smooth, Vascular - drug effects Pharmacology. Drug treatments Pyridines - metabolism Pyridines - pharmacology Rabbits Rats Rats, Sprague-Dawley Rats, Wistar Receptor, Bradykinin B2 Receptors, Bradykinin - metabolism Respiratory system |
| title | Pharmacological characterization of a novel, orally active, nonpeptide bradykinin B2 receptor antagonist, FR167344 |
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