The case of galantamine: repurposing and late blooming of a cholinergic drug

Abstract

Galantamine is a reversible inhibitor of cholinesterases and an allosteric modulator of neuronal nicotinic acetylcholine receptors which restores reduced cholinergic tone in the central and peripheral nervous system. Characterized in the early 1950s in Bulgaria, it saw limited use for paralytic and neuropathic conditions until the cholinergic hypothesis of Alzheimer’s disease opened totally new perspectives for its utility. Although constricted supplies at extremely high prices and a fragmented patent situation made its repurposing challenging, galantamine was globally launched as an Alzheimer’s disease drug in 2000. Many other possible uses have been clinically investigated, and might yet develop into another drug career. This case study is presented as an example for classical on-target drug repurposing and the challenges that such a project can face.