Galanthamine Hydrobromide in a Long-Term Treatment of Alzheimer's Disease

Abstract

We investigated the long-term administration of galanthamine hydrobromide, a cholinesterase inhibitor, in Alzheimer''s disease. The patient was at an advanced stage of the disease and remained unchanged with respect to the results of psychometrical tests. The clinical global impression, however, improved with dosage, and clinical improvement was associated with a remarkable and selective inhibition of acetylcholinesterase activity. Galanthamine was well tolerated without adverse effects or pathological changes in laboratory values, although high doses were given. Intravenous administration of galanthamine to a healthy volunteer revealed that the time course of acetylcholinesterase inhibition and plasma levels of the drug were closely correlated. The pharmacokinetics of galanthamine behaved linearly over the entire dosage range; plasma levels were equal to the concentrations in erythrocytes, and the elimination half-life was even longer than 4.5 h, as described by Westra and co-workers, in anaesthetized patients.

Galanthamine production in ?shoot-clump? cultures of Narcissus confusus in liquid-shake medium

“…Thus, GAL has been shown to be competitive with other anticholinesterastic 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), GAL shows minor effects like agitation or insomnia (Thomsen et al, 1990), with only moderate acute toxicity (Antonyan et al, 1986).…”

Letters to the editor

“…As THA has a significant side-effect profile, particularly in terms of hepatotoxicity and unwanted peripheral cholinergic activity, we have investigated, in an open pilot study, galanthamine hydro-bromide, an anticholinesterase alkaloid derived from the common snowdrop. There have been a small number of previous studies (eg Rainer et al, 1989;Thomsen et al, 1990;Dal Bianco et al, 1991) which in general reported minor degrees of benefit, although statistically insignificant. As these earlier studies used widely varying doses, we have assessed the therapeutic efficacy and tolerance of a low dose, 30-40 mg/day, against a higher dose, 45-60 mg/day, in patients suffering with probable Alzheimer's disease according to the NINCDS criteria (McKhann et al, 1984).…”

Synthesis of 3H‐, 14C‐, and stable‐isotope‐labelled galantamine

“…The bromo-tritium exchange took place in tetrahydrofuran using a palladium catalyst poisoned with butanethiol in order to avoid a possible reduction of the allylic double bond. HPLC purification and resolution produced tritium-labelled galantamine (6). Recently, a procedure was described to obtain 1-bromogalantamine directly from galantamine, 35 which would avoid the final resolution step.…”

“…from various species of Narcissus. 3,4 Galantamine shows reversible, competitive acetylcholinesterase inhibiting and nicotinic acetylcholinergic receptor modulatory properties [5][6][7] and readily crosses the blood-brain barrier. It is generally accepted that cognitive and functional improvement can be achieved with compounds that increase cholinergic neurotransmission in the central nervous system.…”