quinidine   Click here for help

GtoPdb Ligand ID: 2342

Synonyms: Quinaglute® | Quinidex® | quinidine hydrochloride
Approved drug PDB Ligand Antimalarial Ligand
quinidine is an approved drug (FDA (1950))
Compound class: Natural product
Comment: Quinidine is a stereoisomer of quinine. It acts as a class I antiarrhythmic agent, blocking the fast inward sodium current (INa).

The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
Click here for help

Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

✖

View interactive charts of activity data across species

IUPHAR Pharmacology Education Project (PEP) logo

View more information in the IUPHAR Pharmacology Education Project: quinidine

quinidine is commercially available from our sponsors

2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
Hydrogen bond acceptors 3
Hydrogen bond donors 1
Rotatable bonds 4
Topological polar surface area 45.59
Molecular weight 324.18
XLogP 2.6
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

✖
Canonical SMILES C=CC1CN2CCC1CC2C(c1ccnc2c1cc(OC)cc2)O
Isomeric SMILES C=C[C@H]1CN2CC[C@H]1C[C@@H]2[C@H](c1ccnc2c1cc(OC)cc2)O
InChI InChI=1S/C20H24N2O2/c1-3-13-12-22-9-7-14(13)10-19(22)20(23)16-6-8-21-18-5-4-15(24-2)11-17(16)18/h3-6,8,11,13-14,19-20,23H,1,7,9-10,12H2,2H3/t13-,14-,19+,20-/m0/s1
InChI Key LOUPRKONTZGTKE-LHHVKLHASA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Bardien-Kruger S, Wulff H, Arieff Z, Brink P, Chandy KG, Corfield V. (2002)
Characterisation of the human voltage-gated potassium channel gene, KCNA7, a candidate gene for inherited cardiac disorders, and its exclusion as cause of progressive familial heart block I (PFHBI).
Eur J Hum Genet, 10 (1): 36-43. [PMID:11896454]
2. Bhattacharjee A, Joiner WJ, Wu M, Yang Y, Sigworth FJ, Kaczmarek LK. (2003)
Slick (Slo2.1), a rapidly-gating sodium-activated potassium channel inhibited by ATP.
J Neurosci, 23 (37): 11681-91. [PMID:14684870]
3. Caballero R, Pourrier M, Schram G, Delpón E, Tamargo J, Nattel S. (2003)
Effects of flecainide and quinidine on Kv4.2 currents: voltage dependence and role of S6 valines.
Br J Pharmacol, 138 (8): 1475-84. [PMID:12721103]
4. Engel K, Wang J. (2005)
Interaction of organic cations with a newly identified plasma membrane monoamine transporter.
Mol Pharmacol, 68 (5): 1397-407. [PMID:16099839]
5. Gessner G, Zacharias M, Bechstedt S, Schönherr R, Heinemann SH. (2004)
Molecular determinants for high-affinity block of human EAG potassium channels by antiarrhythmic agents.
Mol Pharmacol, 65 (5): 1120-9. [PMID:15102940]
6. Girard C, Duprat F, Terrenoire C, Tinel N, Fosset M, Romey G, Lazdunski M, Lesage F. (2001)
Genomic and functional characteristics of novel human pancreatic 2P domain K(+) channels.
Biochem Biophys Res Commun, 282 (1): 249-56. [PMID:11263999]
7. Han J, Truell J, Gnatenco C, Kim D. (2002)
Characterization of four types of background potassium channels in rat cerebellar granule neurons.
J Physiol (Lond.), 542 (Pt 2): 431-44. [PMID:12122143]
8. Hill RJ, Duff HJ, Sheldon RS. (1989)
Class I antiarrhythmic drug receptor: biochemical evidence for state-dependent interaction with quinidine and lidocaine.
Mol Pharmacol, 36 (1): 150-9. [PMID:2546048]
9. Kang D, Kim D. (2004)
Single-channel properties and pH sensitivity of two-pore domain K+ channels of the TALK family.
Biochem Biophys Res Commun, 315 (4): 836-44. [PMID:14985088]
10. Milligan CJ, Li M, Gazina EV, Heron SE, Nair U, Trager C, Reid CA, Venkat A, Younkin DP, Dlugos DJ et al.. (2014)
KCNT1 gain of function in 2 epilepsy phenotypes is reversed by quinidine.
Ann Neurol, 75 (4): 581-90. [PMID:24591078]
11. Patel AJ, Maingret F, Magnone V, Fosset M, Lazdunski M, Honoré E. (2000)
TWIK-2, an inactivating 2P domain K+ channel.
J Biol Chem, 275 (37): 28722-30. [PMID:10887187]
12. Schönherr R, Gessner G, Löber K, Heinemann SH. (2002)
Functional distinction of human EAG1 and EAG2 potassium channels.
FEBS Lett, 514 (2-3): 204-8. [PMID:11943152]
13. Sheldon RS, Duff HJ, Thakore E, Hill RJ. (1994)
Class I antiarrhythmic drugs: allosteric inhibitors of [3H] batrachotoxinin binding to rat cardiac sodium channels.
J Pharmacol Exp Ther, 268 (1): 187-94. [PMID:8301556]
14. Snyders J, Knoth KM, Roberds SL, Tamkun MM. (1992)
Time-, voltage-, and state-dependent block by quinidine of a cloned human cardiac potassium channel.
Mol Pharmacol, 41 (2): 322-30. [PMID:1538710]
15. Sánchez-Carranza O, Torres-Rodríguez P, Darszon A, Treviño CL, López-González I. (2015)
Pharmacology of hSlo3 channels and their contribution in the capacitation-associated hyperpolarization of human sperm.
Biochem Biophys Res Commun, 466 (3): 554-9. [PMID:26381170]
16. Tang QY, Zhang Z, Xia XM, Lingle CJ. (2010)
Block of mouse Slo1 and Slo3 K+ channels by CTX, IbTX, TEA, 4-AP and quinidine.
Channels (Austin), 4 (1): 22-41. [PMID:19934650]
17. Tanihara Y, Masuda S, Sato T, Katsura T, Ogawa O, Inui K. (2007)
Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters.
Biochem Pharmacol, 74 (2): 359-71. [PMID:17509534]
18. Wang J. (2016)
The plasma membrane monoamine transporter (PMAT): Structure, function, and role in organic cation disposition.
Clin Pharmacol Ther, 100 (5): 489-499. [PMID:27506881]
19. White NJ, Looareesuwan S, Warrell DA, Chongsuphajaisiddhi T, Bunnag D, Harinasuta T. (1981)
Quinidine in falciparum malaria.
Lancet, 2 (8255): 1069-71. [PMID:6118523]
20. Wrighton DC, Muench SP, Lippiat JD. (2015)
Mechanism of inhibition of mouse Slo3 (KCa 5.1) potassium channels by quinine, quinidine and barium.
Br J Pharmacol, 172 (17): 4355-63. [PMID:26045093]
21. Yamagishi T, Ishii K, Taira N. (1995)
Antiarrhythmic and bradycardic drugs inhibit currents of cloned K+ channels, KV1.2 and KV1.4.
Eur J Pharmacol, 281 (2): 151-9. [PMID:7589202]
22. Yang B, Gribkoff VK, Pan J, Damagnez V, Dworetzky SI, Boissard CG, Bhattacharjee A, Yan Y, Sigworth FJ, Kaczmarek LK. (2006)
Pharmacological activation and inhibition of Slack (Slo2.2) channels.
Neuropharmacology, 51 (4): 896-906. [PMID:16876206]