N-Desmethyl Galanthamine

N-desmethyl Galantamine is an alkaloid that has been found in C. asiaticum and is an active metabolite of galantamine .^1,2,3,4,5 It inhibits acetylcholinesterase (AChE; IC₅₀ = 0.23 ?M) and currents induced by ACh by 64.8% in Xenopus oocytes expressing human α7 nicotinic acetylcholine receptors (nAChRs) when used at a concentration of 100 ?M.² N-desmethyl Galantamine is cytotoxic to MOLT-4 acute lymphoblastic leukemia cells and LMTK alveolar fibroblasts (IC₅₀s = 0.6 and 0.5 ?g/ml, respectively).⁴ It decreases disease severity in a mouse model of acute liver injury induced by carbon tetrachloride when administered at doses of 1 and 10 mg/kg.⁵

1.Kobayashi, S., Ishikawa, H., Kihara, M., et al.Isolation of N-demethylgalanthamine from the bulbs of Crinum asiaticum L. var. japanicum Baker (Amaryllidaceae)Chem. Pharm. Bull.24(10)2553-2555(1976) 2.Kowal, N.M., Indurthi, D.C., Ahring, P.K., et al.Novel approach for the search for chemical scaffolds with activity at both acetylcholinesterase and the α7 nicotinic acetylcholine receptor: A perspective on scaffolds with dual activity for the treatment of neurodegenerative disordersMolecules24(3)446(2019) 3.Maláková, J., Nobilis, M., Svoboda, Z., et al.High-performance liquid chromatographic method with UV photodiode-array, fluorescence and mass spectrometric detection for simultaneous determination of galantamine and its phase I metabolites in biological samplesJ. Chromatogr. B. Analyt. Technol. Biomed. Life Sci.853(1-2)265-274(2007) 4.Weniger, B., Italiano, L., Beck, J.-P., et al.Cytotoxic activity of amaryllidaceae alkaloidsPlanta Med.61(1)77-79(1995) 5.Yang, N., Ko, M., Ahn, M., et al.Hepatoprotective effects of norgalanthamine on carbon tetrachloride induced-hepatotoxicity in miceDrug Chem. Toxicol.(2021)