Description
CPI-1189 is a benzamide with neuroprotective and anti-inflammatory activities. It inhibits phosphorylation of p38 MAPK in IL-1β-stimulated primary rat astrocytes by 70 to 80% when used at concentrations ranging from 10 to 300 nM. CPI-1189 (20 mg/kg per day) reduces TNF-α-induced apoptosis in the corpus callosum and septum, but not in the neocortex or basal ganglia, as well as reduces TNF-α-induced decreases in GFAP levels in isolated rat brain slices. It decreases the latency to find the platform in the Morris water maze, indicating reversal of memory deficits, induced by TNF-α in a rat model of AIDS dementia when administered at a dose of 20 mg/kg per day. CPI-1189 (30 mg/kg per day) reduces crypt loss and decreases the number of ulcers and inflammatory cells in colonic lesions in mouse models of colitis induced by TNBS or dextran sulfate sodium (DSS; ).
in vitro
cpi-1189 could potently inhibit p38-mapk phosphorylation displaying protective action against tumor necrosis factor-alpha (tnfalpha)-induced neurodegeneration. moreover, in primary astrocytes treated with interleukin 1beta, cpi-1189 inhibited p38-mapk phosphorylation at low concentrations [1].
in vivo
to model elevated tnf-alpha in aids dementia complex, tnf-alpha was infused into rats. results showed that the co-administration of cpi-1189 prevented tnf-alpha induced apoptosis. both tnf-alpha and cpi-1189 treatment could suppress glial fibrillary acidic protein staining. tnf-alpha alone did not affect the integrity of the blood-brain barrier significantly, but cpi-1189 treatment increased blood-brain barrier integrity [2].
References
[1] hensley k,robinson ka,pye qn,floyd ra,cheng i,garland wa,irwin i. cpi-1189 inhibits interleukin 1beta-induced p38-mitogen-activated protein kinase phosphorylation: an explanation for its neuroprotective properties neurosci lett.2000 mar 10;281(2-3):179-82.
[2] bjugstad kb,flitter wd,garland wa,philpot rm,kirstein cl,arendash gw. cpi-1189 prevents apoptosis and reduces glial fibrillary acidic protein immunostaining in a tnf-alpha infusion model for aids dementia complex. j neurovirol.2000 dec;6(6):478-91.
[3] clifford db,mcarthur jc,schifitto g,kieburtz k,mcdermott mp,letendre s,cohen ba,marder k,ellis rj,marra cm;neurologic aids research consortium. a randomized
