The genus Cinchona is known for a range of
alkaloids, such as
quinine,
quinidine,
cinchonine, and
cinchonidine. Cinchona bark has been used as an
antimalarial agent for more than 400 years.
Quinine was first isolated in 1820 and is still acknowledged in the
therapy of
chloroquine-resistant
falciparum malaria; in lower dosage
quinine has been used as treatment for leg
cramps since the 1940s. Here we report the effects of the
quinoline derivatives
quinine,
quinidine, and
chloroquine on human adult and fetal muscle
nicotinic acetylcholine receptors (nAChRs). It could be demonstrated that the compounds blocked
acetylcholine (ACh)-evoked responses in Xenopus laevis oocytes expressing the adult nAChR composed of αβδ subunits in a concentration-dependent manner, with a ranked potency of
quinine (IC50 = 1.70 μM),
chloroquine (IC50 = 2.22 μM) and
quinidine (IC50 = 3.96 μM). At the fetal nAChR composed of αβγδ subunits, the IC50 for
quinine was found to be 2.30 μM. The efficacy of the block by
quinine was independent of the ACh concentration. Therefore,
quinine is proposed to inhibit ACh-evoked currents in a non-competitive manner. The present results add to the pharmacological characterization of muscle nAChRs and indicate that
quinine is effective at the muscular nAChRs close to therapeutic blood concentrations required for the
therapy and prophylaxis of
nocturnal leg cramps, suggesting that the clinically proven efficacy of
quinine could be based on targeting nAChRs.