QUINIDINE

First approved in 1921

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H24N2O2
Molecular Weight	324.4168
Optical Activity	( + )
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC=C2N=CC=C([C@H](O)[C@H]3C[C@@H]4CC[N@]3C[C@@H]4C=C)C2=C1

InChI

InChIKey=LOUPRKONTZGTKE-LHHVKLHASA-N

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

HIDE SMILES / InChI

Molecular Formula	C20H24N2O2
Molecular Weight	324.4168
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

Quinidine is a pharmaceutical agent that acts as a class I antiarrhythmic agent (Ia) in the heart. It is a stereoisomer of quinine, originally derived from the bark of the cinchona tree. The drug causes increased action potential duration, as well as a prolonged QT interval. Like all other class I antiarrhythmic agents, quinidine primarily works by blocking the fast inward sodium current (INa). Quinidine's effect on INa is known as a 'use-dependent block'. This means at higher heart rates, the block increases, while at lower heart rates, the block decreases. The effect of blocking the fast inward sodium current causes the phase 0 depolarization of the cardiac action potential to decrease (decreased Vmax). Quinidine also blocks the slowly inactivating, tetrodotoxin-sensitive Na current, the slow inward calcium current (ICA), the rapid (IKr) and slow (IKs) components of the delayed potassium rectifier current, the inward potassium rectifier current (IKI), the ATP-sensitive potassium channel (IKATP) and Ito. Quinidine is also an inhibitor of the cytochrome P450 enzyme 2D6 and can lead to increased blood levels of lidocaine, beta blockers, opioids, and some antidepressants. Quinidine also inhibits the transport protein P-glycoprotein and so can cause some peripherally acting drugs such as loperamide to have central nervous system side effects, such as respiratory depression if the two drugs are coadministered. Quinidine can cause thrombocytopenia, granulomatous hepatitis, myasthenia gravis, and torsades de pointes, so is not used much today. Torsades can occur after the first dose. Quinidine-induced thrombocytopenia (low platelet count) is mediated by the immune system and may lead to thrombocytic purpura. A combination of dextromethorphan and quinidine has been shown to alleviate symptoms of easy laughing and crying (pseudobulbar affect) in patients with amyotrophic lateral sclerosis and multiple sclerosis. This drug is marketed as Nuedexta in the United States. Intravenous quinidine is also indicated for the treatment of Plasmodium falciparum malaria. However, quinidine is not considered the first-line therapy for P. falciparum. The recommended treatments for P. falciparum malaria, according to the Toronto Notes 2008, are a combination of either quinine and doxycycline or atovaquone and proguanil (Malarone). The drug is also effective for the treatment of atrial fibrillation in horses.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Voltage-gated potassium channel subunit Kv1.5 34	Inhibitor 7464		7300.0 nM [IC50]
Potassium voltage-gated channel subfamily D member 2 14	Inhibitor 7464		2200.0 nM [IC50]
Voltage-gated L-type calcium channel alpha-1C subunit 41	Inhibitor 7464	Arrhythmia	19820.0 nM [IC50]
Potassium voltage-gated channel subfamily B member 1 16	Inhibitor 7464
Plasmodium falciparum 67	Inhibitor 7464	Malaria, Plasmodium falciparum	18.0 nM [IC50]
Sodium channel protein type V alpha subunit 47	Inhibitor 7464	Atrial Fibrillation	6900.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Malaria, Plasmodium falciparum 14	Primary	Plasmodium falciparum	Approved 7888	QUINIDINE GLUCONATE
Arrhythmia 29	Primary	Voltage-gated L-type calcium channel alpha-1C subunit	Approved 7888	QUINIDINE GLUCONATE
Atrial Fibrillation 140	Primary	Sodium channel protein type V alpha subunit	Approved 7888	QUINIDINE GLUCONATE

PubMed

Title	Date	PubMed
TASK-3, a new member of the tandem pore K(+) channel family.	2000 Mar 31	10734076
Alteration of drug kinetics in rats following exposure to trichloroethylene.	2001	11490201
Pharmacokinetic interactions of antimalarial agents.	2001	11432537
Evaluation of drug-induced QT interval prolongation: implications for drug approval and labelling.	2001	11419561
CIBIS, MERIT-HF, and COPERNICUS trial outcomes: do they complete the chapter on beta-adrenergic blockers as antiarrhythmic and antifibrillatory drugs?	2001 Apr	11509916
HPTLC method for the estimation of alkaloids of Cinchona officinalis stem bark and its marketed formulations.	2001 Apr	11345710
Quinidine and malaria.	2001 Apr 23	11322855
Angiotensin II type I receptor modulates intracellular free Mg2+ in renally derived cells via Na+-dependent Ca2+-independent mechanisms.	2001 Apr 27	11278387
Binding constant determination of drugs toward subdomain IIIA of human serum albumin by near-infrared dye-displacement capillary electrophoresis.	2001 Aug	11519955
[Pharmacokinetics and drug interactions of antidepressive agents].	2001 Aug	11519155
Escitalopram (S-citalopram) and its metabolites in vitro: cytochromes mediating biotransformation, inhibitory effects, and comparison to R-citalopram.	2001 Aug	11454728
Single oral loading dose of propafenone for pharmacological cardioversion of recent-onset atrial fibrillation.	2001 Feb	11216976
Effect of coadministered drugs and ethanol on the binding of therapeutic drugs to human serum in vitro.	2001 Feb	11206047
Characterization of a novel cationic drug transporter in human retinal pigment epithelial cells.	2001 Feb	11160630
Modulation of P450 CYP3A4-dependent metabolism by P-glycoprotein: implications for P450 phenotyping.	2001 Feb	11160617
From the Centers for Disease Control and Prevention. Availability and use of parenteral quinidine gluconate for severe or complicated malaria.	2001 Feb 14	11236771
A human lymphocyte based ex vivo assay to study the effect of drugs on P-glycoprotein (P-gp) function.	2001 Jan	11336351
Species plays an important role in drug-induced prolongation of action potential duration and early afterdepolarizations in isolated Purkinje fibers.	2001 Jan	11204092
Sympathetic activation enhances QT prolongation by quinidine.	2001 Jan	11204091
How do I prolong QT? Let me count the ways.	2001 Jan	11204077
Transport of [3H]MPP+ in an immortalized rat brain microvessel endothelial cell line (RBE 4).	2001 Jan	11191826
A novel zidovudine uptake system in microglia.	2001 Jan	11123374
Evaluation of a vincristine resistant Caco-2 cell line for use in a calcein AM extrusion screening assay for P-glycoprotein interaction.	2001 Jan	11113639
Salt and cosolvent effects on ionic drug loading into microspheres using an O/W method.	2001 Jan 29	11166417
Improved intestinal absorption of sulpiride in rats with synchronized oral delivery systems.	2001 Jan 29	11166414
Effect of mdr1a P-glycoprotein gene disruption, gender, and substrate concentration on brain uptake of selected compounds.	2001 Jul	11496955
A direct injection capillary electrophoretic technique for miniaturized high-throughput metabolic screening of the CYP 3A4 enzyme using quinidine as a probe.	2001 Jul	11377054
In vitro stimulation of warfarin metabolism by quinidine: increases in the formation of 4'- and 10-hydroxywarfarin.	2001 Jun	11353757
Ascorbic acid-induced modulation of venous tone in humans.	2001 Mar	11244023
Acute canine model for drug-induced Torsades de Pointes in drug safety evaluation-influences of anesthesia and validation with quinidine and astemizole.	2001 Mar	11222883
Moxifloxacin: clinical efficacy and safety.	2001 Mar 1	11258173
Effect of hydrophilic substances on liberation of quinidine from starch - alginate sphere.	2001 Mar-Apr	11501786
Metabolism of amiodarone (Part III): identification of rabbit cytochrome P450 isoforms involved in the hydroxylation of mono-N-desethylamiodarone.	2001 May	11491386
Quinidine as an antiarrhythmic.	2001 May	11348982
Interactions between antiarrhythmic drugs and cardiac memory.	2001 May	11334837
Coumarin substrates for cytochrome P450 2D6 fluorescence assays.	2001 May 15	11355862
Drug block of I(kr): model systems and relevance to human arrhythmias.	2001 Nov	11602820
Inhibition of cytochrome P4502D6 activity with paroxetine normalizes the ultrarapid metabolizer phenotype as measured by nortriptyline pharmacokinetics and the debrisoquin test.	2001 Oct	11673748
GAT2/BGT-1 as a system responsible for the transport of gamma-aminobutyric acid at the mouse blood-brain barrier.	2001 Oct	11598501
In vitro effect of alkaloids on bloodstream forms of Trypanosoma brucei and T. congolense.	2001 Oct	11582539
In vitro metabolism of tegaserod in human liver and intestine: assessment of drug interactions.	2001 Oct	11560869
An amino acid residue whose change by mutation affects drug binding to the HERG channel.	2001 Oct 12	11602243
Alkaline phosphatase from rat liver and kidney is differentially modulated.	2001 Sep	11676975
Metabolism of vanoxerine, 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine, by human cytochrome P450 enzymes.	2001 Sep	11502731
Purinoreceptors are involved in the control of acute morphine withdrawal.	2001 Sep 21	11669461

Patents

Sample Use Guides

In Vivo Use Guide

Tablet (sulfate):100 to 600 mg/dose orally every 4 to 6 hours; begin at 200 mg/dose and titrate to desired effect (maximum daily dose: 3 to 4 g). Extended Release: 324 to 648 mg (gluconate) orally every 8 to 12 hours or 300 to 600 mg (sulfate) orally every 8 to 12 hours. IV: 800 mg of quinidine gluconate diluted to 50 mL and given at a rate not to exceed 1 mL/min.

Route of Administration: Oral; intramuscular;

In Vitro Use Guide

Rat brain pericytes were plated onto the backside of 12-well Transwell filters (pore size: 0.4 μm; 1.5 × 104 cells/filter). The next day, endothelial cells were plated onto the upper surface of the filters. After reaching confluency, the endothelial monolayer was supplied with 550 nM hydrocortisone, 250 μM CPT-cAMP, and 17.5 μM RO-201724 and placed into dishes containing glial cultures for 24 h. Transwell filters containing endothelial cells and pericytes were removed from the plates containing the glial culture. Filters were washed with Ringer-HEPES solution (pH 7.4). Quinidine or digoxin was applied at final concentrations of 0.1 μM and 10 μM, respectively. Radiolabeled quinidine and digoxin as tracers were also added to the radioactive concentration of 1 μCi/mL. The inhibitors were added together with the test compound at final concentrations of 1 μM (LY- 335979 and PSC-833) or 100 μM (quinidine). Samples were taken from the basolateral or apical side, respectively, at 15, 30, and 60 min, and radioactivity was measured using a liquid scintillation counter

Substance Class	Chemical Created by `admin` on `Mon Oct 21 22:34:48 UTC 2019` Edited by `admin` on `Mon Oct 21 22:34:48 UTC 2019`
Record UNII	ITX08688JL
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

QUINIDINE

Common Name

English

(+)-QUINIDINE

Common Name

English

(9S)-6'-METHOXYCINCHONAN-9-OL

Systematic Name

English

QUINIDINE [MART.]

Common Name

English

QUINIDINE [WHO-DD]

Common Name

English

.BETA.-QUINIDINE

Common Name

English

CONQUININE

Common Name

English

CINCHONAN-9-OL, 6'-METHOXY-, (9S)-

Common Name

English

QUININE HYDROCHLORIDE IMPURITY A [EP]

Common Name

English

QUININE SULFATE IMPURITY A [EP]

Common Name

English

(8R,9S)-QUINIDINE

Common Name

English

QUINIDINE [VANDF]

Common Name

English

(S)-((2S,4S,5R)-5-ETHENYL-1-AZABICYCLO(2.2.2)OCT-2-YL)(6-METHOXYQUINOLIN-4-YL)METHANOL

Systematic Name

English

QUININE BISULFATE IMPURITY A [WHO-IP]

Common Name

English

QUININE BISULFATE HEPTAHYDRATE IMPURITY A [WHO-IP]

Common Name

English

PITAYINE

Common Name

English

QUININE SULFATE IMPURITY A [WHO-IP]

Common Name

English

QUINIDINE [HSDB]

Common Name

English

QUINIDINE [MI]

Common Name

English

KINIDIN

Common Name

English

Classification Tree Code System Code

WHO-VATC

QC01BA01