A nitric oxide-donating flurbiprofen derivative reduces neuroinflammation without interacting with galantamine in the rat.

Abstract	Alzheimer's disease is associated with glial activation and increased levels of the cytokines as well as impaired forebrain cholinergic function. Current therapies focus on enhancing cholinergic function by administrating acetylcholinesterase inhibitors, such as galantamine. Epidemiological results also suggest that anti-inflammatory therapies might be effective in slowing the onset of the symptoms of Alzheimer's disease. The current study investigated the ability of a nitric oxide (NO)-donating derivative of the nonsteroidal anti-inflammatory drug (NSAID) flurbiprofen, HCT1026, to reduce brain inflammation in young rats. Inflammation was produced by chronic infusion of lipopolysaccharide (LPS) into the 4th ventricle. The release of NO from HCT1026 requires the action of esterase enzymes. The current study determined whether the effectiveness of HCT1026 was attenuated by simultaneous treatment with the acetylcholinesterase inhibitor galantamine. Daily administration of the HCT1026 significantly reduced microglial activation and these effects were not attenuated by galantamine therapy.
Authors	Gary L Wenk, Susanna Rosi, Kristin McGann, Beatrice Hauss-Wegrzyniak
Journal	European journal of pharmacology (Eur J Pharmacol) Vol. 453 Issue 2-3 Pg. 319-24 (Oct 25 2002) ISSN: 0014-2999 [Print] Netherlands
PMID	12398920 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Anti-Inflammatory Agents, Non-Steroidal Cholinesterase Inhibitors Nitric Oxide Donors Galantamine nitroflurbiprofen Flurbiprofen
Topics	Animals Anti-Inflammatory Agents, Non-Steroidal (pharmacology, therapeutic use) Binding Sites Brain (metabolism) Cholinesterase Inhibitors (therapeutic use) Dentate Gyrus (cytology, drug effects, immunology) Drug Therapy, Combination Encephalitis (drug therapy) Flurbiprofen (analogs & derivatives, pharmacology, therapeutic use) Galantamine (therapeutic use) Immunohistochemistry Male Microglia (metabolism) Nitric Oxide Donors (pharmacology, therapeutic use) Radioligand Assay Rats Rats, Inbred F344

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