2-3-dihydro-1-4-phthalazinedione and Shock--Septic

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.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Interleukin-1; Luminol; Macrophages; Male; Mice; Mice, Inbred Strains; Pain Threshold; Receptors, Interleukin-1; Shock, Septic; Tumor Necrosis Factor-alpha