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. Acetylcholine is a key neurotransmitter that regulates many functions in the CNS, as well as in other body organs, through the cholinergic system. Galantamine is a well-known alkaloid drug that modulates this system toward a higher cholinergic tone, and has been put to several therapeutic uses during the past decades, most recently, for Alzheimer's disease. However, its known actions might allow repurposing toward even more applications not only in psychiatry and neurology but also in eye medicine and even in immunology. This article summarizes the claims, the evidence and the potential of galantamine beyond its currently approved uses.