Cholinergic drugs potentiate human nicotinic alpha4beta2 acetylcholine receptors by a competitive mechanism.

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Smulders CJ, Zwart R, Bermudez I, van Kleef RG, Groot-Kormelink PJ, Vijverberg HP

Cholinergic drugs potentiate human nicotinic alpha4beta2 acetylcholine receptors by a competitive mechanism.

Eur J Pharmacol. 2005 Feb 21;509(2-3):97-108.

PubMed ID

15733544 [ View in PubMed

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Abstract

Effects of cholinergic drugs on human alpha4beta2 nicotinic acetylcholine receptors expressed in Xenopus oocytes have been investigated in electrophysiological and ligand binding experiments. Atropine, scopolamine, physostigmine, and tacrine combine potentiation of ion current induced by low concentrations of acetylcholine with inhibition of ion current evoked by high concentrations of acetylcholine. Rivastigmine, galanthamine, and dichlorvos cause only inhibition of ion current evoked by low concentrations of acetylcholine. Binding experiments show that the potentiating cholinergic drugs atropine, scopolamine, and physostigmine are competitive ligands of human alpha4beta2 nicotinic acetylcholine receptors. Conversely, the inhibitory cholinergic drugs galanthamine and rivastigmine are non-competitive. The non-competitive drugs are not allosteric, since they do not affect the saturation curve of the radioligand [3H]cytisine. Effects of potentiating cholinergic drugs on nicotinic acetylcholine receptors are consistent with and predicted by a model comprising competitive drug effects at two equivalent agonist recognition sites on the nicotinic acetylcholine receptor combined with non-competitive ion channel block.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Atropine	Neuronal acetylcholine receptor subunit alpha-4	Protein	Humans	Unknown	Not Available	Details
Atropine	Neuronal acetylcholine receptor subunit beta-2	Protein	Humans	Unknown	Not Available	Details
Scopolamine	Neuronal acetylcholine receptor subunit alpha-4	Protein	Humans	Unknown	Inhibitor Inducer	Details
Scopolamine	Neuronal acetylcholine receptor subunit beta-2	Protein	Humans	Unknown	Inhibitor Inducer	Details