Document Detail


Positive interaction of the beta2-agonist CHF 4226.01 with budesonide in the control of bronchoconstriction induced by acetaldehyde in the guinea-pigs.
MedLine Citation:
PMID:  15655502     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Giuseppe Rossoni; Barbara Manfredi; Roberta Razzetti; Maurizio Civelli; Stefano Bongrani; Ferruccio Berti
Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  British journal of pharmacology     Volume:  144     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-02-07     Completed Date:  2005-06-13     Revised Date:  2013-06-11    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  422-9     Citation Subset:  IM    
Affiliation:
Department of Pharmacological Sciences, University of Milan, Milan, Italy, USA. giuseppe.rossoni@unimi.it
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MeSH Terms
Descriptor/Qualifier:
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*
Guinea Pigs
Histamine / blood
Hydroxyquinolines / pharmacology*
Inosine Triphosphate / pharmacology
Male
Quinolones
Substance P / pharmacology
Chemical
Reg. No./Substance:
0/Adrenergic beta-2 Receptor Agonists; 0/Adrenergic beta-Agonists; 0/Amphetamines; 0/Bronchodilator Agents; 0/Ethanolamines; 0/Ethylamines; 0/Hydroxyquinolines; 0/Quinolones; 132-06-9/Inosine Triphosphate; 147568-66-9/carmoterol; 33507-63-0/Substance P; 51-45-6/Histamine; 51333-22-3/Budesonide; 5ZZ84GCW8B/formoterol; 75-07-0/Acetaldehyde
Comments/Corrections

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