In vitro effects of the antiallergy compound, CI-949, on interleukin-1 and 2 release, and on mitogen and alloantigen responsiveness.
CI-949 (5-methoxy-3-(1-methylethoxy)-1-phenyl-N-1H-tetrazol-5-yl-1H -indole- 2-carboxamide, L-arginine salt), an antiallergy compound, was found to be a weak inhibitor of IL-1 release from LPS-stimulated murine peritoneal exudate cells and human peripheral blood leukocytes, with IC50S of 186.2 and 267.9 microM, respectively. CI-949 was also a poor inhibitor of release of IL-2 from Con A-stimulated rat splenocytes (37% inhibition at 100 microM). CI-949 did produce concentration-related inhibition of the response of human lymphocytes to PHA and Con A (IC50S = 44.7 and 21.5 microM, respectively) as well as in the mixed lymphocyte reaction (MLR) (IC50 = 16.8 microM). The clinical significance of these latter findings is unknown at present.
Gilbertsen
R B
RB
Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105.
Cullinen
K M
KM
Wilburn
D J
DJ
Dong
M K
MK
Conroy
M C
MC
D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism; D001393:Azoles / Q000494:pharmacology*; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007375:Interleukin-1 / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D007519:Isoantigens / Q000276:immunology*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008934:Mitogens / Q000494:pharmacology*; D051381:Rats; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*
D001393:Azoles; D007211:Indoles; D007375:Interleukin-1; D007376:Interleukin-2; D007519:Isoantigens; D008934:Mitogens; D013777:Tetrazoles; C061320:CI 949