0000000000420127
AUTHOR
Claudia Christner
Galantamine is an allosterically potentiating ligand of neuronal nicotinic but not of muscarinic acetylcholine receptors.
Galantamine (Reminyl), an approved treatment for Alzheimer's disease (AD), is a potent allosteric potentiating ligand (APL) of human alpha 3 beta 4, alpha 4 beta 2, and alpha 6 beta 4 nicotinic receptors (nAChRs), and of the chicken/mouse chimeric alpha 7/5-hydroxytryptamine3 receptor, as was shown by whole-cell patch-clamp studies of human embryonic kidney-293 cells stably expressing a single nAChR subtype. Galantamine potentiates agonist responses of the four nAChR subtypes studied in the same window of concentrations (i.e., 0.1-1 microM), which correlates with the cerebrospinal fluid concentration of the drug at the recommended daily dosage of 16 to 24 mg. At concentrations10 microM, gal…
Synthesis and in vitro evaluation of galanthamine derivatives for examination of nicotinic acetylcholine receptor system
ISunmrary: The syntheses and radioactive labeling of several galanthamine derivatives, 6-O-demethyl-6-O-fluoroethylgalanthamine, 10-N-demethyl-lO-Nfluoroethylgalanthamine and N-methylgalanthaminium are reported. First ill vitro evaluations were carried out to determine their properties as allosterically potentiating ligands of nicotinic receptors. N-methylgalanthaminium was found to be a promising candidate for further investigations. The most commonly applied therapeutic approach to balance nicotinic cholinergic deficits in Alzheimer’s disease (AD) patients is the administration of acetylcholinesterase inhibitors (AChE-I) although they have been proven to be of limited therapeutic value [ …
Synthesis and evaluation of tritium labelled 10-methylgalanthamine iodide: a novel compound to examine the mechanism of interaction of galanthamine derivatives with the nicotinic acetylcholine receptors
Summary A new promising galanthamine derivative, 10-[ 3 H]methylgalanthamine iodide, was synthesized for binding studies to nicotinic acetylcholine receptors expressed in Torpedo electric ray electroplaques. Galanthamine was reacted with [ 3 H]methyl iodide to yield 10-[ 3 H]methylgalanthamine iodide with a radiochemical yield of >70% and a specific activity of 32 Ci/mmol after purification via solid phase extraction. To test the ligand properties of the radioligand, calcium imaging and electrophysiology of the non-radioactive analogue were performed to obtain an EC50 of 270 nM, a Hill coefficient of 1.9 and the induced cell current. Copyright # 2003 John Wiley & Sons, Ltd.