Positive interaction of the beta2-agonist CHF 4226.01 with budesonide in the control of bronchoconstriction induced by acetaldehyde in the guinea-pigs
Pretreatment of anaesthetized guinea-pigs with either CHF 4226.01 (8-hydroxy-5-[(1R)-1-hydroxy-2-[N-[(1R)-2-(p-methoxyphenyl)-1-methylethyl]amino]ethyl] carbostyril hydrochloride), formoterol or budesonide reduced acetaldehyde (AcCHO)-evoked responses in the lungs with a rank order of potency CHF 42...
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| Veröffentlicht in: | British journal of pharmacology 2005-02, Vol.144 (3), p.422 |
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| creator | Rossoni, Giuseppe Manfredi, Barbara Razzetti, Roberta Civelli, Maurizio Bongrani, Stefano Berti, Ferruccio |
| description | Pretreatment of anaesthetized guinea-pigs with either CHF 4226.01 (8-hydroxy-5-[(1R)-1-hydroxy-2-[N-[(1R)-2-(p-methoxyphenyl)-1-methylethyl]amino]ethyl] carbostyril hydrochloride), formoterol or budesonide reduced acetaldehyde (AcCHO)-evoked responses in the lungs with a rank order of potency CHF 4226.01 (ED(50) values, from 1.88 to 3.31 pmol) > formoterol (ED(50) values, from 3.03 to 5.51 pmol) >> budesonide (ED(50) values, from 335 to 458 nmol). The duration of action of CHF 4226.01 in antagonizing the airway obstruction elicited by AcCHO was also substantially longer than formoterol (area under the curve) at 10 pmol, 763+/-58 and 480+/-34, respectively; P |
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The duration of action of CHF 4226.01 in antagonizing the airway obstruction elicited by AcCHO was also substantially longer than formoterol (area under the curve) at 10 pmol, 763+/-58 and 480+/-34, respectively; P<0.01). Continuous infusion of a subthreshold dose of AcCHO enhanced the intratracheal pressure (ITP) increases caused by subsequent challenges with substance P (from 9.7+/-0.8 to 27.5+/-1.6 cm H(2)O as a peak, P<0.001). Pretreatment with either CHF 4226.01 or formoterol prevented the sensitizing effect of AcCHO on substance P responses (ED(50) values, 2.85 and 6.11 pmol, respectively; P<0.01). The ED(50) value of budesonide (396 nmol) in preventing AcCHO-evoked ITP increase was reduced when this glucocorticoid was combined with 0.1 pmol CHF 4226.01 (ED(50) 76 nmol; P<0.001). CHF 4226.01/budesonide was two-fold more effective (P<0.01) than the formoterol/budesonide combination. These results suggest that CHF 4226.01/budesonide, by optimizing each other's beneficial potential in the control of pulmonary changes caused by AcCHO in the guinea-pigs, may represent a new fixed combination in asthma.</description><identifier>ISSN: 0007-1188</identifier><identifier>PMID: 15655502</identifier><language>eng</language><publisher>England</publisher><subject>Acetaldehyde - pharmacology ; Adrenergic beta-2 Receptor Agonists ; Adrenergic beta-Agonists - pharmacology ; Amphetamines ; Animals ; Bronchoconstriction - drug effects ; Bronchodilator Agents - pharmacology ; Budesonide - pharmacology ; Capillary Permeability - drug effects ; Dose-Response Relationship, Drug ; Drug Synergism ; Ethanolamines - pharmacology ; Ethylamines - pharmacology ; Formoterol Fumarate ; Guinea Pigs ; Histamine - blood ; Hydroxyquinolines - pharmacology ; Inosine Triphosphate - pharmacology ; Male ; Quinolones ; Substance P - pharmacology</subject><ispartof>British journal of pharmacology, 2005-02, Vol.144 (3), p.422</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15655502$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rossoni, Giuseppe</creatorcontrib><creatorcontrib>Manfredi, Barbara</creatorcontrib><creatorcontrib>Razzetti, Roberta</creatorcontrib><creatorcontrib>Civelli, Maurizio</creatorcontrib><creatorcontrib>Bongrani, Stefano</creatorcontrib><creatorcontrib>Berti, Ferruccio</creatorcontrib><title>Positive interaction of the beta2-agonist CHF 4226.01 with budesonide in the control of bronchoconstriction induced by acetaldehyde in the guinea-pigs</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>Pretreatment of anaesthetized guinea-pigs with either CHF 4226.01 (8-hydroxy-5-[(1R)-1-hydroxy-2-[N-[(1R)-2-(p-methoxyphenyl)-1-methylethyl]amino]ethyl] carbostyril hydrochloride), formoterol or budesonide reduced acetaldehyde (AcCHO)-evoked responses in the lungs with a rank order of potency CHF 4226.01 (ED(50) values, from 1.88 to 3.31 pmol) > formoterol (ED(50) values, from 3.03 to 5.51 pmol) >> budesonide (ED(50) values, from 335 to 458 nmol). The duration of action of CHF 4226.01 in antagonizing the airway obstruction elicited by AcCHO was also substantially longer than formoterol (area under the curve) at 10 pmol, 763+/-58 and 480+/-34, respectively; P<0.01). Continuous infusion of a subthreshold dose of AcCHO enhanced the intratracheal pressure (ITP) increases caused by subsequent challenges with substance P (from 9.7+/-0.8 to 27.5+/-1.6 cm H(2)O as a peak, P<0.001). Pretreatment with either CHF 4226.01 or formoterol prevented the sensitizing effect of AcCHO on substance P responses (ED(50) values, 2.85 and 6.11 pmol, respectively; P<0.01). The ED(50) value of budesonide (396 nmol) in preventing AcCHO-evoked ITP increase was reduced when this glucocorticoid was combined with 0.1 pmol CHF 4226.01 (ED(50) 76 nmol; P<0.001). CHF 4226.01/budesonide was two-fold more effective (P<0.01) than the formoterol/budesonide combination. These results suggest that CHF 4226.01/budesonide, by optimizing each other's beneficial potential in the control of pulmonary changes caused by AcCHO in the guinea-pigs, may represent a new fixed combination in asthma.</description><subject>Acetaldehyde - pharmacology</subject><subject>Adrenergic beta-2 Receptor Agonists</subject><subject>Adrenergic beta-Agonists - pharmacology</subject><subject>Amphetamines</subject><subject>Animals</subject><subject>Bronchoconstriction - drug effects</subject><subject>Bronchodilator Agents - pharmacology</subject><subject>Budesonide - pharmacology</subject><subject>Capillary Permeability - drug effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Synergism</subject><subject>Ethanolamines - pharmacology</subject><subject>Ethylamines - pharmacology</subject><subject>Formoterol Fumarate</subject><subject>Guinea Pigs</subject><subject>Histamine - blood</subject><subject>Hydroxyquinolines - pharmacology</subject><subject>Inosine Triphosphate - pharmacology</subject><subject>Male</subject><subject>Quinolones</subject><subject>Substance P - pharmacology</subject><issn>0007-1188</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0EtOwzAQgGEvQLQUroB8gSB7HOexRBWlSJVg0X3lsZ3GqLWj2AHlIpyXlBaxGmlG37-YKzJnjJUZ51U1I7cxfjDG87KUN2TGZSGlZDAn3-8huuQ-LXU-2V7p5IKnoaGptRRtUpCpffAuJrpcr2gOUDwyTr9caikOxsbpZk74F-jgUx8OJ4998LoN0yam3p2zzptBW0NxpEpP7YOx7fiv94PzVmWd28c7ct2oQ7T3l7kg29XzdrnONm8vr8unTdbJHLIaBCBUBQfZMJZX2AguGq4F1GiZ5ChqYWoOppINYlUUIPRkUEswaKAUC_JwznYDHq3Zdb07qn7c_f1H_ABDN2GR</recordid><startdate>200502</startdate><enddate>200502</enddate><creator>Rossoni, Giuseppe</creator><creator>Manfredi, Barbara</creator><creator>Razzetti, Roberta</creator><creator>Civelli, Maurizio</creator><creator>Bongrani, Stefano</creator><creator>Berti, Ferruccio</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>200502</creationdate><title>Positive interaction of the beta2-agonist CHF 4226.01 with budesonide in the control of bronchoconstriction induced by acetaldehyde in the guinea-pigs</title><author>Rossoni, Giuseppe ; Manfredi, Barbara ; Razzetti, Roberta ; Civelli, Maurizio ; Bongrani, Stefano ; Berti, Ferruccio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p542-9232b286125f0048bf313f1c329be051b393d912d85fbb86623c923bc52dbd273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Acetaldehyde - pharmacology</topic><topic>Adrenergic beta-2 Receptor Agonists</topic><topic>Adrenergic beta-Agonists - pharmacology</topic><topic>Amphetamines</topic><topic>Animals</topic><topic>Bronchoconstriction - drug effects</topic><topic>Bronchodilator Agents - pharmacology</topic><topic>Budesonide - pharmacology</topic><topic>Capillary Permeability - drug effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Synergism</topic><topic>Ethanolamines - pharmacology</topic><topic>Ethylamines - pharmacology</topic><topic>Formoterol Fumarate</topic><topic>Guinea Pigs</topic><topic>Histamine - blood</topic><topic>Hydroxyquinolines - pharmacology</topic><topic>Inosine Triphosphate - pharmacology</topic><topic>Male</topic><topic>Quinolones</topic><topic>Substance P - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rossoni, Giuseppe</creatorcontrib><creatorcontrib>Manfredi, Barbara</creatorcontrib><creatorcontrib>Razzetti, Roberta</creatorcontrib><creatorcontrib>Civelli, Maurizio</creatorcontrib><creatorcontrib>Bongrani, Stefano</creatorcontrib><creatorcontrib>Berti, Ferruccio</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rossoni, Giuseppe</au><au>Manfredi, Barbara</au><au>Razzetti, Roberta</au><au>Civelli, Maurizio</au><au>Bongrani, Stefano</au><au>Berti, Ferruccio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Positive interaction of the beta2-agonist CHF 4226.01 with budesonide in the control of bronchoconstriction induced by acetaldehyde in the guinea-pigs</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>2005-02</date><risdate>2005</risdate><volume>144</volume><issue>3</issue><spage>422</spage><pages>422-</pages><issn>0007-1188</issn><abstract>Pretreatment of anaesthetized guinea-pigs with either CHF 4226.01 (8-hydroxy-5-[(1R)-1-hydroxy-2-[N-[(1R)-2-(p-methoxyphenyl)-1-methylethyl]amino]ethyl] carbostyril hydrochloride), formoterol or budesonide reduced acetaldehyde (AcCHO)-evoked responses in the lungs with a rank order of potency CHF 4226.01 (ED(50) values, from 1.88 to 3.31 pmol) > formoterol (ED(50) values, from 3.03 to 5.51 pmol) >> budesonide (ED(50) values, from 335 to 458 nmol). The duration of action of CHF 4226.01 in antagonizing the airway obstruction elicited by AcCHO was also substantially longer than formoterol (area under the curve) at 10 pmol, 763+/-58 and 480+/-34, respectively; P<0.01). Continuous infusion of a subthreshold dose of AcCHO enhanced the intratracheal pressure (ITP) increases caused by subsequent challenges with substance P (from 9.7+/-0.8 to 27.5+/-1.6 cm H(2)O as a peak, P<0.001). Pretreatment with either CHF 4226.01 or formoterol prevented the sensitizing effect of AcCHO on substance P responses (ED(50) values, 2.85 and 6.11 pmol, respectively; P<0.01). The ED(50) value of budesonide (396 nmol) in preventing AcCHO-evoked ITP increase was reduced when this glucocorticoid was combined with 0.1 pmol CHF 4226.01 (ED(50) 76 nmol; P<0.001). CHF 4226.01/budesonide was two-fold more effective (P<0.01) than the formoterol/budesonide combination. These results suggest that CHF 4226.01/budesonide, by optimizing each other's beneficial potential in the control of pulmonary changes caused by AcCHO in the guinea-pigs, may represent a new fixed combination in asthma.</abstract><cop>England</cop><pmid>15655502</pmid></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Access via Wiley Online Library; Wiley Online Library (Open Access Collection); PubMed Central; Alma/SFX Local Collection |
| subjects | Acetaldehyde - pharmacology Adrenergic beta-2 Receptor Agonists Adrenergic beta-Agonists - pharmacology Amphetamines Animals Bronchoconstriction - drug effects Bronchodilator Agents - pharmacology Budesonide - pharmacology Capillary Permeability - drug effects Dose-Response Relationship, Drug Drug Synergism Ethanolamines - pharmacology Ethylamines - pharmacology Formoterol Fumarate Guinea Pigs Histamine - blood Hydroxyquinolines - pharmacology Inosine Triphosphate - pharmacology Male Quinolones Substance P - pharmacology |
| title | Positive interaction of the beta2-agonist CHF 4226.01 with budesonide in the control of bronchoconstriction induced by acetaldehyde in the guinea-pigs |
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