Narcissus and Daffodil

13 Compounds from the genus Narcissus:
pharmacology, pharmacokinetics and
toxicology
David Brown
INTRODUCTION
The genus Narcissus has yielded several useful or potentially useful compounds,
although just one of them, galanthamine, has been investigated in any great
detail. As with most modern phytopharmaceuticals, identification, purification
and investigation of the active principles have only been accomplished after many
years, perhaps centuries, of folk medicine use as whole plant material or crude
extracts. For the earliest account of a clinical use of galanthamine one has to go
back to ancient Greek times. Homer’s Odyssey has it that the attempts of Circe to
poison Odysseus were foiled when Hermes gave Odysseus an antidotal root drawn
from the earth, with a black root and milk-like flower, which was difficult for mortals
to dig up and which the gods called ‘moly’. On the basis of descriptions of their
symptoms (memory loss, hallucinations and delusions that they had been turned
into pigs) it has been suggested that the drug which Circe had used to poison
Odysseus’ men was a powerful, centrally acting, anticholinergic drug called
stramonium, derived from the common plant Datura stramonium. The story is told
much more eloquently by Plaitakis and Duvoisin (1983) who postulate that the
antidote was derived from the common snowdrop, Galanthus nivalis, which contains
the anticholinesterase, galanthamine. This is based on the description of the
antidote or ‘moly’ given by Homer and by later Greek texts and recognition that
both plants (Datura and Galanthus) would have been a resource native to the area.
The authors state that if all this were true, then it represents the oldest recorded
use of an anticholinesterase to reverse anticholinergic intoxication.
Of course, these accounts refer to snowdrop, not narcissus, but galanthamine
is a derivative common to both. Originally isolated from Galanthus nivalis and used
clinically under the name ‘Nivalin’, galanthamine can also be derived from
Narcissus cultivars (Moraes-Cerdeira et al., 1997) and represents the most pharmacologically
interesting and to date, clinically useful compound, to be derived from
the genus. There is at the time of writing, considerable interest in galanthamine as
a potential treatment for Alzheimer’s disease. This chapter reviews the pharmacology,
pharmacokinetics and toxicology of galanthamine in animals and man. The
rationale behind its various putative clinical uses is also discussed. Reference is also
made to another interesting compound, pretazettine, which has been investigated
as an adjunct to cancer chemotherapy. Clinical (phase 2 and 3) trials with galanthamine
in Alzheimer’s disease are discussed in the following chapter of this
volume.