The effects of ML 3000 on antigen-induced responses in sheep

被引:25
作者
Abraham, WM
Laufer, S
Tries, S
机构
[1] Univ Miami, Mt Sinai Med Ctr, Div Pulm & Crit Care Med, Miami Beach, FL 33140 USA
[2] Merckle GMBH, Div Res & Dev, D-89135 Blaubeuren, Germany
关键词
asthma; bronchoconstriction; late response; therapy; cyclooxygenase; 5-lipoxygenase;
D O I
10.1006/pupt.1997.0090
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
ML 3000 is a dual inhibitor of cyclooxygenase (COX) and 5-lipoxygenase (5-LO), two enzymes that contribute to the airway inflammation in asthma. When administered as an aerosol at a dose of 100 mg, 0.5 h before antigen challenge in allergic sheep, ML 3000 provided significant inhibition against the early bronchial response (EAR, mean 33% protection, P<0.05), completely blocked the late antigen-induced bronchoconstriction (LAR, mean 81% protection, P<0.05) and the airway hyperresponsiveness (AHR, P<0.05) to aerosolized carbachol that occurs 24 h after antigen challenge in this model. Consistent with this functional protection was a small but significant reduction in the percentage of neutrophils recovered in bronchoalveolar lavage (BAL) at 8 h and 24 h after challenge. These findings are similar to previous data obtained in this animal model with other 5-LO inhibitors (blockade of the LAR and AHR) and COX inhibitors (blockade of AHR). These results suggest that aerosol administration of a dual inhibitor of COX and 5-LO may have beneficial effects in the treatment of allergic airway disease. (C) 1997 Academic Press Limited.
引用
收藏
页码:167 / 173
页数:7
相关论文
共 54 条
[21]  
FAIRFAX AJ, 1983, CLIN EXP IMMUNOL, V52, P393
[22]   EFFECT OF CHRONIC 5-LIPOXYGENASE INHIBITION ON AIRWAY HYPERRESPONSIVENESS IN ASTHMATIC SUBJECTS [J].
FISCHER, AR ;
MCFADDEN, CA ;
FRANTZ, R ;
AWNI, WM ;
COHN, J ;
DRAZEN, JM ;
ISRAEL, E .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1995, 152 (04) :1203-1207
[23]   BRONCHOCONSTRICTOR AND ANTIBRONCHOCONSTRICTOR PROPERTIES OF INHALED PROSTACYCLIN IN ASTHMA [J].
HARDY, CC ;
BRADDING, P ;
ROBINSON, C ;
HOLGATE, ST .
JOURNAL OF APPLIED PHYSIOLOGY, 1988, 64 (04) :1567-1574
[24]   Leukotriene antagonists and synthesis inhibitors: New directions in asthma therapy [J].
Holgate, ST ;
Bradding, P ;
Sampson, AP .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1996, 98 (01) :1-13
[25]   PHARMACOLOGY OF MONTELUKAST SODIUM (SINGULAIR(TM)), A POTENT AND SELECTIVE LEUKOTRIENE D-4 RECEPTOR ANTAGONIST [J].
JONES, TR ;
LABELLE, M ;
BELLEY, M ;
CHAMPION, E ;
CHARETTE, L ;
EVANS, J ;
FORDHUTCHINSON, AW ;
GAUTHIER, JY ;
LORD, A ;
MASSON, P ;
MCAULIFFE, M ;
MCFARLANE, CS ;
METTERS, KM ;
PICKETT, C ;
PIECHUTA, H ;
ROCHETTE, C ;
RODGER, IW ;
SAWYER, N ;
YOUNG, RN ;
ZAMBONI, R ;
ABRAHAM, WM .
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 1995, 73 (02) :191-201
[26]  
KAWAKAMI Y, 1993, EUR J CLIN PHARMACOL, V6, P127
[27]   EFFECT OF INDOMETHACIN ON ALLERGEN-INDUCED ASTHMATIC RESPONSES [J].
KIRBY, JG ;
HARGREAVE, FE ;
COCKCROFT, DW ;
OBYRNE, PM .
JOURNAL OF APPLIED PHYSIOLOGY, 1989, 66 (02) :578-583
[28]  
KNAPP HR, 1992, J LAB CLIN MED, V119, P48
[29]   INDOMETHACIN AND FPL-57231 INHIBIT ANTIGEN-INDUCED AIRWAY HYPERRESPONSIVENESS IN SHEEP [J].
LANES, S ;
STEVENSON, JS ;
CODIAS, E ;
HERNANDEZ, A ;
SIELCZAK, MW ;
WANNER, A ;
ABRAHAM, WM .
JOURNAL OF APPLIED PHYSIOLOGY, 1986, 61 (03) :864-872
[30]  
LAUFER S, 1995, ARZNEIMITTEL-FORSCH, V45-1, P27