Antagonism of leukotriene responses in human airways by BAY x7195.
Contractions induced by leukotriene and anti-IgE (sheep antiserum to human IgE) were antagonized by pretreatment of human airways with the cysteinyl leukotriene receptor antagonist BAY x7195 ((4S)-[4-carboxyphenylthio]-7-[4-(4-phenoxybutoxy)-phenyl]-h ept-5-(z)- enoic acid). However, this receptor antagonist did not inhibit either leukotriene D4- or leukotriene C4-induced contractions in human pulmonary veins. The pA2 value for BAY x7195 in human airways against leukotriene D4 was 7.83 +/- 0.16 with a slope of 1.07 +/- 0.15 (means +/- S.E.M; n = 11). The IC50 value for BAY x7195 in human airways contracted with anti-IgE was 0.31 +/- 0.08 microM (n = 11). These results were comparable to those obtained with ICI 204,219 (4-(5-cyclopentyl-oxycarbonylamino-1-methylindol-3-ylmeth yl)-3-methoxy-N-otolyl - sulfonylbenzamide). These data demonstrate that BAY x7195 is a potent selective leukotriene receptor antagonist which may block allergic reactions in the lung.
Gorenne
I
I
Bayer plc, Pharmaceutical Business Group, Research Department, UK.
Ortiz
J L
JL
Labat
C
C
Abram
T
T
Tudhop
S
S
Cuthbert
N
N
Norman
P
P
Gardiner
P
P
Morcillo
E
E
Brink
C
C
D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006880:Hydroxy Acids / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000276:immunology; D007211:Indoles; D017997:Leukotriene C4 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D017998:Leukotriene D4 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D048448:Phenylcarbamates; D011667:Pulmonary Veins / Q000187:drug effects / Q000378:metabolism; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000494:pharmacology
D000888:Antibodies, Anti-Idiotypic; D001993:Bronchodilator Agents; D006880:Hydroxy Acids; D007211:Indoles; D048448:Phenylcarbamates; D013449:Sulfonamides; D014105:Tosyl Compounds; C026408:anti-IgE antibodies; D017997:Leukotriene C4; D007073:Immunoglobulin E; D017998:Leukotriene D4; C092294:BAY x 7195; C062735:zafirlukast