General Description
A competitive and reversible inhibitor of acetylcholinesterase. Antimyasthenic agent. Can partially reverse the effects of scopolamine-induced amnesia in rats. Reported to improve learning and short-term memory in animal models.
Biochem/physiol Actions
Primary TargetAcetylcholinesterase
Clinical Use
Galantamine, which was introduced in 2001, is an alkaloid found in plants of the family Amaryllidaceae, which includes the daffodil (Narcissus
pseudonarcissus) and snowflake (Leucojum aestivum). It is a reversible inhibitor of AChE, but it does not appear to inhibit butyrylcholinesterase.
Because it is a tertiary amine and can cross the blood-brain barrier, it is indicated for treatment of mild-to-moderate AD and dementia. It has
been used outside the U.S. for more than 30 years as an anticurare agent in anesthesia. Galantamine differs from other cholinesterase
inhibitors, because it allosterically binds to nicotinic receptors, giving it a dual cholinergic action.
Metabolism
It is metabolized (75%) by CYP2D6 and
CYP3A4 to afford the normethyl, O-desmethyl, and O-desmethylnormethyl metabolites, along with some other minor metabolites. Unlike tacrine,
galantamine is not associated with hepatotoxicity. Its elimination half-life is 5.7 hours.
