The effects of inhaled KP-496, a novel dual antagonist for cysteinyl leukotriene receptor and thromboxane A(2) receptor, on allergic asthmatic responses in guinea pigs.
Pharmacology
; 84(4): 249-56, 2009.
Article
em En
| MEDLINE
| ID: mdl-19776661
ABSTRACT
AIMS:
The aim of this study was to evaluate the effects of inhaled KP-496, a novel dual antagonist for cysteinyl leukotriene receptor 1 and thromboxane A(2) receptor, on the allergic asthmatic responses in guinea pigs.METHODS:
Actively sensitized animals were repeatedly exposed to antigen, and KP-496 (0.01 and 0.1%) was inhaled for 5 min before every antigen exposure. After evaluating the effects of KP-496 on asthmatic responses, such as immediate and late asthmatic response (IAR and LAR) and airway hyperresponsiveness (AHR), histopathological analyses of the lungs of asthmatic animals were made.RESULTS:
KP-496 significantly inhibited both antigen-induced LAR and AHR to acetylcholine, and slightly inhibited antigen-induced IAR. Furthermore, histopathological analyses of the lungs of the asthmatic animals demonstrated the following (1) KP-496 suppressed infiltration of eosinophils around airway smooth muscle, (2) KP-496 suppressed airway epithelial hypertrophy, and (3) KP-496 suppressed increased mucus production in the airway.CONCLUSION:
In addition to suppression of LAR and AHR, our findings demonstrated that KP-496 inhibits features of airway inflammation. Since these broad ameliorative effects of KP-496 on asthmatic pathology are thought to result from the inhibition of multiple chemical mediators, KP-496 will be a potent agent in the treatment of bronchial asthma.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Tiazóis
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Benzoatos
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Receptores de Leucotrienos
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Antiasmáticos
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Receptores de Tromboxano A2 e Prostaglandina H2
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article