Narcissus and Daffodil

Pharmacology of Narcissus compounds 333
PHARMACOLOGY OF GALANTHAMINE
Galanthamine was first isolated in Russia in 1947 and its structure was determined
in Japan some five years later (Prokurnina and Yakovleva, 1952; Uyeo and
Kobayashi, 1953). A milestone in the development of galanthamine came in the
early 1960s, when the compound was first recognised as a reversible inhibitor of
acetylcholinesterase (Boissier et al., 1960; Irwin and Smith, 1960a). Soon after this,
evidence was provided that the drug could cross the blood-brain barrier (Nesterenko,
1964).
In the 1960s and 1970s, the drug was used in eastern bloc countries for a range
of neurological disorders (see Clinical Applications, below) but because of the cold
war, much of the early literature remained obscure. This, and the fact that galanthamine
was available only as a natural product from limited Bulgarian and Turkish
sources, explains why Western investigators were slow to appreciate and investigate
its potential.
Galanthamine, a tertiary alkaloid (see Figure 13.1), is a selective and reversible
inhibitor of anticholinesterase, which is an enzyme responsible for the degradation
of acetylcholine at the neuromuscular junction. The detailed animal pharmacology
has been reviewed elsewhere (Harvey, 1995). Essentially, galanthamine has
been shown to inhibit both dog skeletal muscle in vitro and cat and mouse brain
anticholinesterase in vivo and in vitro in micromolar quantities. When compared
HO
H
O
O
CH 3
N
CH 3
N
O
OH
1-adamantyl demethyl galanthamine
O
galanthamine
OCH 3
O
O
HO
CH 3
N
O
morphine
OH
O
pretazettine
OCH 3
H
OH
N CH 3
Figure 13.1 Chemical structures for galanthamine, morphine, 1-adamantyl demethyl
galanthamine and pretazettine.