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.
Positive interaction of the beta2-agonist CHF 4226.01 with budesonide in the control of bronchoconstriction induced by acetaldehyde in the guinea-pigs / G. Rossoni, B. Manfredi, R. Razzetti, M. Civelli, S. Bongrani, F. Berti. - In: BRITISH JOURNAL OF PHARMACOLOGY. - ISSN 0007-1188. - 144:3(2005), pp. 422-429.
|Titolo:||Positive interaction of the beta2-agonist CHF 4226.01 with budesonide in the control of bronchoconstriction induced by acetaldehyde in the guinea-pigs|
ROSSONI, GIUSEPPE BATTISTA (Primo)
MANFREDI, BARBARA (Secondo)
|Parole Chiave:||animal; article; blood; bronchospasm; capillary permeability; comparative study; dose response; drug effect; drug potentiation; guinea pig; male; 8 hydroxy 5 ((1R) 1 hydroxy 2 (N (1R) 2 (p methoxyphenyl) 1 methylethyl)amino)ethyl carbostyril hydrochloride; 8-hydroxy-5-((1R)-1-hydroxy-2-(N-(1R)-2-(p-methoxyphenyl)-1-methylethyl)amino)ethyl carbostyril hydrochloride; acetaldehyde; beta 2 adrenergic receptor; beta adrenergic receptor stimulating agent; bronchodilating agent; budesonide; ethanolamine derivative; ethylamine; formoterol; histamine; inosine triphosphate; quinolinol derivative; substance P|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||2005|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/sj.bjp.0706096|
|Appare nelle tipologie:||01 - Articolo su periodico|