Galanthamine

Galanthamine is a potent acetylcholinesterase (AChE) inhibitor with an IC₅₀ of 500 nM. IC50 & Target: IC50: 0.5 μM (AChE)^[1] In Vitro: Galanthamine inhibits AChE and BChE with IC₅₀ of 0.5 and 8.5 μM^[1]. Galanthamine acts as a positive allosteric modulator (PAM) of human α4β2 AChRs 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]. In Vivo: Acute administration of Galantamine (0.3-3 mg/kg, i.p.) increases IGF2 mRNA levels in the hippocampus, but not in the prefrontal cortex, in time- and dose-dependent manner. Galantamine (3 mg/kg, i.p.) causes 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 does not affect the mRNA levels of other neurotrophic/growth factors. The Galantamine-induced increase in the hippocampal IGF2 mRNA levels is blocked by Mecamylamine, a nonselective nicotinic acetylcholine (ACh) receptor (nAChR) antagonist, and Methyllycaconitine, a selective α7 nAChR antagonist, but not by Telenzepine, a preferential M1muscarinic ACh receptor antagonist. Moreover, the selective α7 nAChR agonist PHA-543613 increasea the IGF2 mRNA levels, while Donepezil, an acetylcholinesterase inhibitor, does not. Galantamine also increases hippocampal IGF2 protein, which is blocked by Methyllycaconitine^[2].