Preclinical studies with galanthamine

This chapter summarizes early investigations concerned with galanthamine 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 Alzheimer's disease. The compound was first used by Bulgarian and Russian researchers in the 1950s, and much of the original literature of this time is, therefore, not easily accessible. Consistent with the contemporary 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 injury. As early as 1972, Soviet researchers had demonstrated that galanthamine could reverse scopolamine-induced amnesia in mice, a finding that 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 developed at this time is that it was available only in very limited amounts. Although its chemical structure was known, and a laboratory-scale synthesis of very low yield had been developed by 1960, all supplies came from natural extracts until very recently.