This chapter summarizes early investigations concerned with galanthami
ne hydrobromide, a well-tolerated morphine alkaloid with acetylcholine
esterase inhibitor activity that has been exploited for a variety of
clinical purposes in the past, and which is now being developed for Al
zheimer's disease. The compound was first used by Bulgarian and Russia
n researchers in the 1950s, and much of the original literature of thi
s time is, therefore, not easily accessible. Consistent with the conte
mporary practices, few safety and efficacy studies had been conducted
before it was routinely used for postsurgery reversal of tubocurarine-
induced muscle relaxation, muscular dystrophy and traumatic brain inju
ry. As early as 1972, Soviet researchers had demonstrated that galanth
amine could reverse scopolamine-induced amnesia in mice, a finding tha
t was extended to man 4 years later. However, this did not lead to the
application of this compound in Alzheimer's disease until 1986, long
after the cholinergic hypothesis of Alzheimer's disease had been first
postulated. One of the reasons why galanthamine was not properly deve
loped at this time is that it was available only in very limited amoun
ts. Although its chemical structure was known, and a laboratory-scale
synthesis of very low yield had been developed by 1960, all supplies c
ame from natural extracts until very recently.