Ganstigmine (CHF 2819 free base) is a potent, orally active, blood-brain barrier-permeable acetylcholinesterase ( AChE ) inhibitor, with an IC 50 value of 65 nM against human AChE , 310 nM against human butyrylcholinesterase ( BChE ), and 5.12 μM against Torpedo californica AChE . Ganstigmine increases extracellular acetylcholine levels in the brain of rodents without altering the concentrations of other neurotransmitters, stimulates cholinergic transmission, and induces the release of soluble non-amyloidogenic amyloid precursor protein. Ganstigmine exhibits neuroprotective activity independent of cholinesterase inhibition, prevents neuronal death, alleviates β-amyloid-induced neurodegeneration, rescues cholinergic neuron loss, and reverses Scopolamine (HY-N0296)-induced amnesia and memory deficits. Ganstigmine shows cholinesterase inhibition-independent neuroprotective effects against growth factor deprivation and Aβ 25-35 toxicity. Ganstigmine can be used in research on Alzheimer's disease, cholinergic dysfunction, and neuroprotection.
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