Galantamine, a new treatment strategy for Alzheimer’s disease

Allosteric sensitization of nicotinic receptors by galantamine , a new treatment strategy for Alzheimer’s disease.

Maelicke A, Samochocki M, Jostock R, Fehrenbacher A, Ludwig J, Albuquerque EX

Laboratory of Molecular Neurobiology,
Institute of Physiological Chemistry and Pathobiochemistry,
Johannes-Gutenberg University Medical School, Mainz, Germany
Biol Psychiatry 2001;49:279-88.

Abstract

Cholinesterase inhibitors are the only approved drug treatment for patients with mild to moderately severe Alzheimer’s disease. Interestingly, the clinical potency of these drugs does not correlate well with their activity as cholinesterase inhibitors, nor is their action as short lived as would be expected from purely symptomatic treatment. A few cholinesterase inhibitors, including galantamine, produce beneficial effects even after drug treatment has been terminated. These effects assume modes of action other than mere esterase inhibition and are capable of inducing systemic changes. We have recently discovered a mechanism that could account, at least in part, for the above-mentioned unexpected properties of some cholinesterase inhibitors. We have found that a subgroup of cholinesterase inhibitors, including galantamine but excluding tacrine, directly interacts with nicotinic acetylcholine receptors. These compounds, named allosterically potentiating ligands, sensitize nicotinic receptors by increasing the probability of channel opening induced by acetylcholine and nicotinic agonists and by slowing down receptor desensitization. The allosterically potentiating ligand action, which is not necessarily associated with cholinesterase inhibition, has been demonstrated by whole-cell patch-clamp recordings to occur in natural murine and human neurons and in murine and human cell lines expressing various subtypes of neuronal nicotinic acetylcholine receptors.

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Research abstracts
Galantamine: its use in Alzheimer’s
Galantamine: in Alzheimer’s patients
Galantamine: acetylcholinesterase inhibition
Galantamine: therapeutic effects beyond cognition
Galantamine: benefits to Alzheimer’s patients
Galantamine: nicotinic receptors modulation in Alzheimers’s
Galantamine: a study in Alzheimer’s
Galantamine: its effects on Alzheimer’s
Galantamine: a new treatment for Alzheimer’s
Galantamine: effect on nicotinic receptor binding
Galantamine: an allosterically potentiating ligant
Galantamine: nicotinic modulation in an animal model
Galantamine: memory & nicotinic receptors effect in rats
Galantamine: a 6 month study: