Narcissus and Daffodil

14 Galanthamine: clinical trials
in Alzheimer’s disease
David Brown
INTRODUCTION
The isolation, and subsequent chemical, pharmacological and toxicological characterisation
of galanthamine, is described in the previous chapter of this volume,
together with a summary of trials in indications other than Alzheimer’s Disease
(AD). This chapter reviews the early trials of galanthamine in AD and provides
detail, where it is available, of ongoing clinical research with the compound. For a
review of the animal work underpinning this application, the reader is referred to
the previous chapter.
The development of galanthamine has been slow and clinically multi-faceted,
but it is far from a dinosaur drug. At the time of writing, at least three pharmaceutical
companies are developing the drug for the AD market on an international
basis. Waldheim Pharmazeutika (Austria) has developed a method of synthesis
that is feasible on an industrial scale. Shire Pharmaceuticals (England) has filed
patents and is conducting extensive clinical trials with an allied company, Janssen
Pharmaceutica (Belgium). The understandable reluctance of these companies to
reveal unpublished data for inclusion in this review is evidence of the highly
competitive atmosphere surrounding galanthamine.
BRIEF OVERVIEW OF ALZHEIMER’S DISEASE
AD is the most common form of dementia, accounting for 50–70% of all cases
(Rossor, 1996) and is an important cause of morbidity and premature death in the
elderly, worldwide. Typically, patients experience a slow but inexorable decline in
memory and cognitive function, which eventually leads to complete dependency
on family and professional carers and death, on average 4–6 years from diagnosis
with a spread of 2–10 years. Early symptoms include short-term memory loss,
progressing to confusion and disorientation with intermittent periods of lucidity,
which often make the disease more painful to bear for patients and carers alike. As
AD progresses, gross personality changes and emotional disintegration may occur.
In long-standing disease, the patient may be mute, inattentive and completely
incapable of self-care. Late psychiatric symptoms include hallucinations, agitation
and aggression. Death commonly results from the complications of immobility
such as bronchopneumonia; a definitive diagnosis of AD requires post-mortem