title: 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.affiliation: Division of Neural Systems, Memory and Aging, University of Arizona, 384 Life Sciences North Building, Tucson, AZ 85724, USA. gary@nsma.arizona.edu
authors.forename: Gary L
authors.initials: GL
authors.lastname: Wenk
authors.forename: Susanna
authors.initials: S
authors.lastname: Rosi
authors.forename: Kristin
authors.initials: K
authors.lastname: McGann
authors.forename: Beatrice
authors.initials: B
authors.lastname: Hauss-Wegrzyniak
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D004359:Drug Therapy, Combination; D004660:Encephalitis / Q000188:drug therapy*; D005480:Flurbiprofen / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D005702:Galantamine / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology / Q000627:therapeutic use*; D011869:Radioligand Assay; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002800:Cholinesterase Inhibitors; D020030:Nitric Oxide Donors; D005702:Galantamine; C095631:nitroflurbiprofen; D005480:Flurbiprofen