Galanthamine is a long-acting, centrally active acetylcholinesterase (AChE) inhibitor (IC50 = 410 nM) and allosteric potentiator at neuronal nicotinic ACh receptors.
Galanthamine is selective for acetylcholinesterase versus butyrylcholinesterase. Galanthamine attenuates drug-and lesion-induced cognitive deficits in animal models of learning and memory[1]. Galanthamine acts as a positive allosteric modulator (PAM) of human α4β2 AChRs (accessory subunits in heteromeric nicotinic receptors) expressed in permanently transfected HEK 293 cells. Galanthamine increases the response of (α4β2)2α5 AChRs to 1 μM ACh by up to 220% with very low concerntration(EC50=0.25 nM). Only small potentiation (20%) of either α4β2 or (α4β2)2β3 AChRs is detected using FLEXstation assays. Galanthamine at concentrations of 1 μM and above inhibits all three AChR subtypes[2]. Acute administration of galantamine (0.3-3 mg/kg, i.p.) increased IGF2 mRNA levels in the hippocampus, but not in the prefrontal cortex, in time- and dose-dependent manner. Galantamine (3 mg/kg, i.p.) caused a transient increase in fibroblast growth factor 2 mRNA levels and a decrease in brain-derived neurotrophic factor mRNA levels in the hippocampus, while it did not affect the mRNA levels of other neurotrophic/growth factors[3]. Galantamine treatment prevented LPS-induced (lipopolysaccharide) deficits in spatial learning and memory as well as memory acquisition of the passive avoidance response. Galantamine reduced the inflammatory response not only in the BV-2 microglia cell line, but also in the HT-22 hippocampal neuronal cell line[4].
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