Anti-inflammatory activity of 2,3-dihydrophthalazine-1,4-diones in CF1 mice.
2,3-Dihydrophthalazine-1,4-diones were observed to be potent anti-inflammatory agents as well as capable of protecting against endotoxin shock in mice at 8 mg/kg i.p. These agents blocked both locally- and centrally-induced pain at 8 mg/kg i.p. In part they appear to mediate their effects due to their ability to suppress the release of cytokines such as TNF alpha and IL-1 from macrophages, as well as the binding of these cytokines to high-affinity receptors on target cells involved in the inflammation process. Lysosomal hydrolytic enzymes as well as 5'-lipoxygenase activities were reduced by the agents.
Butner
L
L
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27559-7360, USA.
Huang
Y
Y
Tse
E
E
Hall
I H
IH
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D007375:Interleukin-1 / Q000378:metabolism; D008165:Luminol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D017288:Pain Threshold / Q000187:drug effects; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D012772:Shock, Septic / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha; C058828:2,3-dihydro-1,4-phthalazinedione; D008165:Luminol