Effects of Quinine, Quinidine, and Chloroquine on α9α10 Nicotinic Cholinergic Receptors

@article{Ballestero2005EffectsOQ,
  title={Effects of Quinine, Quinidine, and Chloroquine on $\alpha$9$\alpha$10 Nicotinic Cholinergic Receptors},
  author={J. Ballestero and P. Plazas and S. Kracun and M. E. G{\'o}mez-Casati and Julian Taranda and C. Rothlin and E. Katz and N. Millar and A. Elgoyhen},
  journal={Molecular Pharmacology},
  year={2005},
  volume={68},
  pages={822 - 829}
}
In this study, we report the effects of the quinoline derivatives quinine, its optical isomer quinidine, and chloroquine on α9α10-containing nicotinic acetylcholine receptors (nAChRs). The compounds blocked acetylcholine (ACh)-evoked responses in α9α10-injected Xenopus laevis oocytes in a concentration-dependent manner, with a rank order of potency of chloroquine (IC50 = 0.39 μM) > quinine (IC50 = 0.97 μM) ∼ quinidine (IC50 = 1.37 μM). Moreover, chloroquine blocked ACh-evoked responses on rat… Expand

Figures and Tables from this paper

Effects of Quinine, Quinidine and Chloroquine on Human Muscle Nicotinic Acetylcholine Receptors
TLDR
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 nA ChRs. Expand
Tricyclic antidepressants inhibit hippocampal α7* and α9α10 nicotinic acetylcholine receptors by different mechanisms.
TLDR
The molecular docking and functional results support the notion that imipramine noncompetitively inhibits α7 AChRs by interacting with two overlapping luminal sites, whereas it competitively inhibitsAlpha7, α9α10, and hippocampal α7* A ChRs at clinically relevant concentrations and by different mechanisms of action. Expand
The Antimalarial Drug Proguanil Is an Antagonist at 5-HT3 Receptors
TLDR
It is demonstrated that proguanil competitively inhibits 5-HT3 receptors, with an IC50 that exceeds whole-blood concentrations following its oral administration, which may be responsible for the occasional gastrointestinal side effects, nausea, and vomiting reported following its use. Expand
Selectivity of (±)-citalopram at nicotinic acetylcholine receptors and different inhibitory mechanisms between habenular α3β4* and α9α10 subtypes
TLDR
Electrophysiological, molecular docking, and in silico mutation results indicate that (±)-citalopram competitively inhibits rα9α10 AChRs and inhibits habenular α3β4*AChRs, supporting the notion that these receptors are important endogenous targets related to their anti-addictive activities. Expand
The 5-HT3 receptor as a therapeutic target
TLDR
The structure, function and distribution of 5-HT3 receptors and how this may influence their role in disease are looked at. Expand
Triphenylphosphine oxide is a potent and selective inhibitor of the transient receptor potential melastatin-5 ion channel.
TLDR
triphenylphosphine oxide (TPPO) is the most potent TRPM5 inhibitor described to date and is the first demonstrated to exhibit selectivity over other channels. Expand
(E)-3-Furan-2-yl-N-p-tolyl-acrylamide and its Derivative DM489 Decrease Neuropathic Pain in Mice Predominantly by α7 Nicotinic Acetylcholine Receptor Potentiation.
TLDR
The electrophysiological results support the notion that α7 nAChR potentiation is likely the predominant molecular mechanism underlying the observed anti-nociceptive pain activity of these compounds. Expand
5-HT(3) receptors: role in disease and target of drugs.
TLDR
The actual state of the pharmacological knowledge concerning not only classical 5-HT(3) antagonists--the setrons--but also compounds of various substance classes targeting 5- HT( 3) receptors such as anaesthetics, opioids, cannabinoids, steroids, antidepressants and antipsychotics as well as natural compounds derived from plants are focused on. Expand
Neuronal Nicotinic Receptors: One Hundred Years of Progress
TLDR
This chapter reviews some of the fundamental aspects of nicotinic receptors, with emphasis on the differences in pharmacology among the receptor subtypes and their unusual regulation by exposure to nicotine. Expand
The effects of chloroquine and hydroxychloroquine on ACE2 related coronavirus pathology and the cardiovascular system: An evidence based review
  • Li Chen, Haiyan Chen, +23 authors Guang Hao
  • Medicine
  • Function (Oxford, England)
  • 2020
TLDR
CQ and HCQ could potentially be useful drugs in the treatment of COVID-19 and other ACE2 involved virus infections, but the antiviral effects of CQ andHCQ need to be tested in more well-designed clinical randomized studies and their actions on the cardiovascular system need to been further elucidated. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 46 REFERENCES
Effects of the quinoline derivatives quinine, quinidine, and chloroquine on neuromuscular transmission
TLDR
Because quinoline drugs adversely affect both presynaptic and postsynaptic aspects of neuromuscular transmission at concentrations close to those employed in clinical practice, they should not be used, or used with caution, in disorders that compromise the safety margin of neuromechanical transmission. Expand
Block of the α9 nicotinic receptor by ototoxic aminoglycosides
TLDR
The present results suggest that the initial reversible actions of aminoglycosides at the organ of Corti, such as the elimination of the olivocochlear efferent function, are due in part to the interaction with the native α9-containing cholinergic receptor of the outer hair cells. Expand
Effects of quinine on the excitability and voltage-dependent currents of isolated spiral ganglion neurons in culture.
TLDR
Quinine-induced tinnitus may be explained by its broadening of action potentials while the drug's inhibition on INa may result in hearing loss by making the conversion from excitatory postsynaptic potentials to the generation ofaction potentials more difficult. Expand
The α9α10 nicotinic acetylcholine receptor is permeable to and is modulated by divalent cations
Abstract The native cholinergic receptor that mediates synaptic transmission between olivocochlear fibers and outer hair cells of the cochlea is permeable to Ca2+ and is thought to be composed ofExpand
Dihydropyridines and verapamil inhibit voltage-dependent K+ current in isolated outer hair cells of the guinea pig
TLDR
The observation that relatively low concentrations of calcium channel ligands can directly inhibit potassium currents in isolated OHCs indicates that caution should be taken when these pharmacological agents are used as tools for studying cochlear hair cell physiology. Expand
Salicylate, mefenamate, meclofenamate, and quinine on cochlear potentials
  • Jean-Luc Fuel, R. Bobbin, M. Fallon
  • Medicine
  • Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery
  • 1990
TLDR
The results suggest that salicylate-induced hearing loss is not caused by either antagonism of the hair cell transmitter or cyclooxygenase inhibition, nor is it caused by the same mechanism that causes quinine- induced hearing loss. Expand
Pharmacological Properties of α9α10 Nicotinic Acetylcholine Receptors Revealed by Heterologous Expression of Subunit Chimeras
TLDR
Subunit chimeras have been constructed that contain the extracellular, ligand binding domain of the α9 or α10 subunits fused to the C-terminal domain ofThe 5-hydroxytryptamine type 3A (5HT3A) subunit, providing evidence of a requirement for coassembly of α9 and α10 for the efficient formation of a nicotinic binding site. Expand
Quinidine normalizes the open duration of slow‐channel mutants of the acetylcholine receptor
TLDR
The hypothesis that quinidine can normalize the prolonged channel opening events of slow-channel mutants of human AChR is tested and a therapeutic effect for quInidine in the slow- channel congenital myasthenic syndrome is predicted. Expand
Key roles of hydrophobic rings of TM2 in gating of the α9α10 nicotinic cholinergic receptor
TLDR
A systematic mutagenesis of three hydrophobic rings within transmembrane region (TM) 2 of the α9α10 nicotinic cholinergic receptor (nAChR) to a hydrophilic (threonine) residue was performed and the properties of mutant receptors reconstituted in Xenopus laevis oocytes were compared. Expand
Influence of ototoxic drugs on acetylcholine-induced depression of the cochlear N1 potential.
Abstract Cats were prepared to record from the cochlear round window. The cochlear potential (N 1 ) is depressed by 15–30 μg of acetylcholine administered intra-arterially before and after section ofExpand
...
1
2
3
4
5
...