Review of the acetylcholinesterase inhibitor galanthamine.
Sramek JJ, Frackiewicz EJ, Cutler NR
California Clinical Trials,
8501 Wilshire Boulevard, 2nd Floor,
CA 90211, USA.
Expert Opin Investig Drugs 2000 Oct;9(10):2393-402
Galanthamine (or galantamine, Reminyl) is a
tertiary alkaloid acetylcholinesterase inhibitor (AChEI) which has been approved
in several countries for the symptomatic treatment of senile dementia of the
Alzheimer's type. Derived from bulbs of the common snowdrop and several
Amaryllidaceae plants, (-)-galanthamine (GAL) has long been used in anaesthetics
to reverse neuromuscular paralysis induced by turbocurarine-like muscle
relaxants and more recently, has been shown to attenuate drug- and
lesion-induced cognitive deficits in animal models of learning and memory. GAL
directly inhibits acetylcholinesterase activity, while demonstrating much weaker
activity on butyrylcholinesterase (BuChE). GAL also stimulates pre- and
postsynaptic nicotinic receptors, although the clinical significance of this
finding is yet unclear. Numerous variants and analogues of GAL have also been
developed, with varying potency in inhibiting AChE activity. GAL is readily
absorbed after oral administration, with a t(max) of 52 min and a plasma
elimination t(1/2) of 5.7 h. The efficacy of GAL administered to Alzheimer's
disease (AD) patients has been well demonstrated by large-scale clinical trials.
Typical of AChEIs, the most common adverse events associated with GAL are nausea
and vomiting. In conclusion, evidence to date suggests galanthamine to be
similar to other AChEIs in improving cognitive function in AD patients.