treats mod-severe AD (chol, 5-HT, NA, HA inhibitory neurotransmission decreased, so more NMDA activation)
block NMDA to prevent calcium entry excitotoxicity, and down-regulation of NMDA receptors...restore balance.
also blocks alpha7, 9, 10 nicotonic subunits with ACh receptors, regulates release of glutamate from hippocampus and cortical neurons, non-competitive blockade
also non-competitively blocks 5-HT3 receptors which are ligand-gated ionoropic receptors for cations
intended to destroy insoluble, neurooxic beta-amyloid plaques that leads to inflammatory damage, dysfunction, and death of neurons...but trial withdrawn because 7% of subjects developed aseptic meningoencephalitis.
cholinergic agonist, muscarinic selective
40x greater affinity for M1/M3 than M2
decreases extracellular accumulations of beta-amyloid peptide
may lead to decrease plaque formation
SE: less bradycardia (M2) than phenserine
phenylcarbamate of physosigmine
1. potent AChesterase inhibitor
2. normal fxning of Chol system regulates process of beta-amyloid precursor protein (APP)
therefore, beta-amyloid formation inhibited (same for all AChEs)
ABeta amyloid aggregation inhibitor
could prevent formation of plaques
flavonoids + terpene-lactones + organic/coumaric acid suggested to increase cerebral bf in vitro
thereby inhibits aggregation of amyloid-beta, but only at high concentrations
flavonoids are antioxidants...not proven better than placebo
Vitamin E (alpha-tocopherol)
antioxidant - decrease inflamm around plaques
1000mg/day slow progression of disease?
inhibits breakdown of DA & 5-HT
may improve sx of AD but lacks global effect on disease
should not be given with many drugs
People who take NSAIDs regularly have lower incidence of Alzheimer's disease...but no benefit of treatment with an NSAID to persons with AD already
post-men women on HRT have lower incidence of AD?
but combo of E + P increase chance of stroke (impaired cholesterol)