Narcissus and Daffodil

7 Production of galanthamine
by Narcissus tissues in vitro
Carles Codina
INTRODUCTION
Galanthamine is a morphine-like alkaloid that is a possible therapeutic agent in
Alzheimer’s disease because of its central cholinergic effects (Harvey, 1995). It has
been shown to be competitive with other anticholinesterase compounds like
tacrine or physostigmine in the treatment of the syndrome (Rainer et al., 1989).
In contrast with the proven hepatotoxicity of tacrine (Gauthier et al., 1990), galanthamine
shows only minor side effects like agitation or insommia (Thomsen et al.,
1990). Thus, galanthamine is considered a better therapeutic candidate for the
treatment of this type of senile dementia than other acetylcholinesterase inhibitors
structurally related to it (Bores et al., 1996).
Galanthamine can be extracted from plants of the Amaryllidaceae family, the
main natural sources being species of the genera Galanthus and Leucojum from
Bulgaria and the Caucasus region. Galanthamine is difficult to obtain and extremely
expensive for clinical usage. Although the total synthesis of galanthamine has been
achieved (Czollner et al., 1998), the stereoselectivity of its reactions and the low
yields make this process economically unattractive. Therefore, as the plant remains
the only valid source of galanthamine, a biotechnological approach has been considered
as an alternative method for the production of the alkaloid.
Although much work has been done on the propagation of bulbous plants, very
little exists on the production of secondary metabolites from them, this being
restricted mainly to the production of colchicine by callus culture of Colchicum
autumnale (Hayashi et al., 1988; Yoshida et al., 1988), haemanthamine by root cultures
of Zephyranthes robusta (Furmanova and Oledzka, 1990), and bufadienolides
by different tissues of Urginea indica (Jha et al., 1991).
Investigations at the University of Barcelona with plants of the genus Narcissus
have focused on the propagation of several species by in vitro liquid culture
(Bergoñón et al., 1992; Bergoñón, 1994; Riera, 1996; Sellés, 1996), and also on the
production of alkaloids using different explants of Narcissus confusus, a wild species
which was found to contain 0.1% of galanthamine on a fresh weight basis, as well as
other alkaloids including N-formylnorgalanthamine, haemanthamine and tazettine
(Bastida et al., 1987). Experiments dealing with the production of galanthamine
and related alkaloids have been performed using shoot-clumps (meristematic
clusters), which were obtained from two different types of explants, of seed or bulb
origin. These shoot-clumps constitute a good experimental system as they are
made up of differentiated tissue, with a higher expression of secondary metabolism