Galanthamine hydrobromide

The alkaloid (—)-galanthamine, isolated from Caucasian snow-drop Galanthus woronowii) and other plant sources, is a competitive and reversible acetylcholinesterase inhibitor and an allosteric modulator of the neural nicotine receptors for acetylcholine. Galanthamine hydrobromide (commercially available as Razadyne) finds application in the treatment of symptoms of Alzheimer s disease [101]. Since the isolation of galanthamine (256) from natural sources is quite expensive, several total syntheses have been developed to date. The synthetic strategy to galanthamine (256) developed by Cho et al. [102] includes a domino Stille/Diels-Alder reaction as the key step (Scheme 14.39). 

Galanthamine was reported to exert 50-fold selectivity against AChE than BChE by in vitro and in vivo experiments [28] and shown to inhibit AChE activity in human brain 10-fold less potent than that in human erythrocytes [34]. The pharmacokinetic data obtained from human subjects revealed that application of galanthamine hydrobromide at doses of 5 and 10 mg caused first-order pharmacokinetics, complete oral bioavailabihty, and a mean terminal half-life of 5.68 h [35]. 

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