The effects of a novel series of selective inhibitors of arachidonate 5-lipoxygenase on anaphylactic and inflammatory responses.
In conclusion, we have described a novel series of acetohydroxamic acids that are potent and selective inhibitors of arachidonate 5-lipoxygenase in vitro and in vivo. In addition, we have shown that these compounds attenuate "leukotriene-dependent" anaphylactic bronchospasm, the accumulation of inflammatory leukocytes, and the development of fever in experimental models. It now remains to be determined if these compounds have any therapeutic value in man.
Bhattacherjee
P
P
Wellcome Research Laboratories, Beckenham, Kent, United Kingdom.
Boughton-Smith
N K
NK
Follenfant
R L
RL
Garland
L G
LG
Higgs
G A
GA
Hodson
H F
HF
Islip
P J
PJ
Jackson
W P
WP
Moncada
S
S
Payne
A N
AN
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D000707:Anaphylaxis / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001091:Arachidonate Lipoxygenases / Q000037:antagonists & inhibitors*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001985:Bronchial Provocation Tests; D001986:Bronchial Spasm / Q000503:physiopathology; D005334:Fever / Q000503:physiopathology; D005753:Gastric Mucosa / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007249:Inflammation; D007962:Leukocytes / Q000201:enzymology; D007975:Leukotriene B4 / Q000502:physiology; D016859:Lipoxygenase Inhibitors; D009637:Masoprocol / Q000494:pharmacology; D051381:Rats; D013189:SRS-A / Q000502:physiology
D001095:Arachidonic Acids; D006877:Hydroxamic Acids; D016859:Lipoxygenase Inhibitors; D013189:SRS-A; D015117:5,8,11,14-Eicosatetraynoic Acid; D007975:Leukotriene B4; D016718:Arachidonic Acid; C006358:acetohydroxamic acid; D009637:Masoprocol; D001091:Arachidonate Lipoxygenases; D001094:Arachidonate 5-Lipoxygenase