Abstract
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 αβ𝜀δ 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.
Highlights
Quinoline derivatives such as natural quinine, quinidine, and synthetically produced chloroquine are well known for their use in the treatment of malaria (Figure 1)
We examined the effects of the quinoline derivatives quinine, quinidine, and chloroquine on adult and fetal human muscle nicotinic acetylcholine receptors (nAChRs) recombinantly expressed in X. laevis oocytes and provide evidence that these compounds block the nAChRs
This study describes the effects of quinine, quinidine, and chloroquine on human muscle nAChRs
Summary
Quinoline derivatives such as natural quinine, quinidine, and synthetically produced chloroquine are well known for their use in the treatment of malaria (Figure 1). The muscle relaxant mechanism of action of quinine has not been fully elucidated yet. As it does not freely cross the blood brain barrier (Silamut et al, 1985), quinine is supposed to be a peripheral muscle relaxant in vivo. Quinine and its derivatives are acting on a variety of ion channels including several types of potassium channels (Glavinovicand Trifaró, 1988; Imai et al, 1999), members of family of ligand-gated ion channels such as the 5-HT3-type of serotonin receptor (Thompson et al, 2007; Thompson and Lummis, 2008) and nicotinic acetylcholine receptors (nAChR)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
