QUINIDINE

First marketed in 1921

Details

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

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]1(C[C@@H]2CC[N@]1C[C@@H]2C=C)[C@@H](O)C3=C4C=C(OC)C=CC4=NC=C3

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	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.drugs.com/pro/quinidine.html
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/17506538 | https://www.ncbi.nlm.nih.gov/pubmed/22761000 | https://www.ncbi.nlm.nih.gov/pubmed/22512909 | https://www.ncbi.nlm.nih.gov/pubmed/21832259

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	Potency
Voltage-gated potassium channel subunit Kv1.5 37 Target ID: CHEMBL4306 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17506538	Inhibitor 8228	7300.0 nM [IC50]
Sodium channel protein type V alpha subunit 49 Target ID: CHEMBL1980 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17506538	Inhibitor 8228	6900.0 nM [IC50]
Potassium voltage-gated channel subfamily D member 2 15 Target ID: CHEMBL5885 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17506538	Inhibitor 8228	2200.0 nM [IC50]
Voltage-gated L-type calcium channel alpha-1C subunit 44 Target ID: CHEMBL1940 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22761000	Inhibitor 8228	19820.0 nM [IC50]
Potassium voltage-gated channel subfamily B member 1 17 Target ID: CHEMBL1075226 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17506538	Inhibitor 8228
Plasmodium falciparum 72 Target ID: CHEMBL364 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22512909	Inhibitor 8228	18.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Plasmodium falciparum malaria 63 Sources: https://www.drugs.com/pro/quinidine.html	Primary	Approved 8360	QUINIDINE GLUCONATE Approved Use Conversion of atrial fibrillation/flutter In patients with symptomatic atrial fibrillation/flutter whose symptoms are not adequately controlled by measures that reduce the rate of ventricular response, quinidine sulfate is indicated as a means of restoring normal sinus rhythm. If this use of quinidine sulfate does not restore sinus rhythm within a reasonable time (see ), then quinidine sulfate should be discontinued. DOSAGE AND ADMINISTRATION Reduction of frequency of relapse into atrial fibrillation/flutter Chronic therapy with quinidine sulfate is indicated for some patients at high risk of symptomatic atrial fibrillation/flutter, generally patients who have had previous episodes of atrial fibrillation/flutter that were so frequent and poorly tolerated as to outweigh, in the judgment of the physician and the patient, the risks of prophylactic therapy with quinidine sulfate. The increased risk of death should specifically be considered. Quinidine sulfate should be used only after alternative measures ( use of other drugs to control the ventricular rate) have been found to be inadequate. e.g., In patients with histories of frequent symptomatic episodes of atrial fibrillation/flutter, the goal of therapy should be an increase in the average time between episodes. In most patients, the tachyarrhythmia during therapy, and a single recurrence should not be interpreted as therapeutic failure. will recur Suppression of ventricular arrhythmias Quinidine sulfate is also indicated for the suppression of recurrent documented ventricular arrhythmias, such as sustained ventricular tachycardia, that in the judgment of the physician are life-threatening. Because of the proarrhythmic effects of quinidine, its use with ventricular arrhythmias of lesser severity is generally not recommended, and treatment of patients with asymptomatic ventricular premature contractions should be avoided. Where possible, therapy should be guided by the results of programmed electrical stimulation and/or Holter monitoring with exercise. Antiarrhythmic drugs (including quinidine sulfate) have not been shown to enhance survival in patients with ventricular arrhythmias. Treatment of malaria Quinidine sulfate is also indicated in the treatment of life-threatening malaria. Plasmodium falciparum Launch Date -6.1456318E11
Atrial fibrillation 131 Sources: https://www.drugs.com/pro/quinidine.html	Primary	Approved 8360	QUINIDINE GLUCONATE Approved Use Conversion of atrial fibrillation/flutter In patients with symptomatic atrial fibrillation/flutter whose symptoms are not adequately controlled by measures that reduce the rate of ventricular response, quinidine sulfate is indicated as a means of restoring normal sinus rhythm. If this use of quinidine sulfate does not restore sinus rhythm within a reasonable time (see ), then quinidine sulfate should be discontinued. DOSAGE AND ADMINISTRATION Reduction of frequency of relapse into atrial fibrillation/flutter Chronic therapy with quinidine sulfate is indicated for some patients at high risk of symptomatic atrial fibrillation/flutter, generally patients who have had previous episodes of atrial fibrillation/flutter that were so frequent and poorly tolerated as to outweigh, in the judgment of the physician and the patient, the risks of prophylactic therapy with quinidine sulfate. The increased risk of death should specifically be considered. Quinidine sulfate should be used only after alternative measures ( use of other drugs to control the ventricular rate) have been found to be inadequate. e.g., In patients with histories of frequent symptomatic episodes of atrial fibrillation/flutter, the goal of therapy should be an increase in the average time between episodes. In most patients, the tachyarrhythmia during therapy, and a single recurrence should not be interpreted as therapeutic failure. will recur Suppression of ventricular arrhythmias Quinidine sulfate is also indicated for the suppression of recurrent documented ventricular arrhythmias, such as sustained ventricular tachycardia, that in the judgment of the physician are life-threatening. Because of the proarrhythmic effects of quinidine, its use with ventricular arrhythmias of lesser severity is generally not recommended, and treatment of patients with asymptomatic ventricular premature contractions should be avoided. Where possible, therapy should be guided by the results of programmed electrical stimulation and/or Holter monitoring with exercise. Antiarrhythmic drugs (including quinidine sulfate) have not been shown to enhance survival in patients with ventricular arrhythmias. Treatment of malaria Quinidine sulfate is also indicated in the treatment of life-threatening malaria. Plasmodium falciparum Launch Date -6.1456318E11
Ventricular arrhythmia 50 Sources: https://www.drugs.com/pro/quinidine.html	Primary	Approved 8360	QUINIDINE GLUCONATE Approved Use Conversion of atrial fibrillation/flutter In patients with symptomatic atrial fibrillation/flutter whose symptoms are not adequately controlled by measures that reduce the rate of ventricular response, quinidine sulfate is indicated as a means of restoring normal sinus rhythm. If this use of quinidine sulfate does not restore sinus rhythm within a reasonable time (see ), then quinidine sulfate should be discontinued. DOSAGE AND ADMINISTRATION Reduction of frequency of relapse into atrial fibrillation/flutter Chronic therapy with quinidine sulfate is indicated for some patients at high risk of symptomatic atrial fibrillation/flutter, generally patients who have had previous episodes of atrial fibrillation/flutter that were so frequent and poorly tolerated as to outweigh, in the judgment of the physician and the patient, the risks of prophylactic therapy with quinidine sulfate. The increased risk of death should specifically be considered. Quinidine sulfate should be used only after alternative measures ( use of other drugs to control the ventricular rate) have been found to be inadequate. e.g., In patients with histories of frequent symptomatic episodes of atrial fibrillation/flutter, the goal of therapy should be an increase in the average time between episodes. In most patients, the tachyarrhythmia during therapy, and a single recurrence should not be interpreted as therapeutic failure. will recur Suppression of ventricular arrhythmias Quinidine sulfate is also indicated for the suppression of recurrent documented ventricular arrhythmias, such as sustained ventricular tachycardia, that in the judgment of the physician are life-threatening. Because of the proarrhythmic effects of quinidine, its use with ventricular arrhythmias of lesser severity is generally not recommended, and treatment of patients with asymptomatic ventricular premature contractions should be avoided. Where possible, therapy should be guided by the results of programmed electrical stimulation and/or Holter monitoring with exercise. Antiarrhythmic drugs (including quinidine sulfate) have not been shown to enhance survival in patients with ventricular arrhythmias. Treatment of malaria Quinidine sulfate is also indicated in the treatment of life-threatening malaria. Plasmodium falciparum Launch Date -6.1456318E11

C_max

Value	Dose	Co-administered	Analyte	Population
3.4 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/512840/	3.74 mg/kg single, oral dose: 3.74 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		QUINIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
12.8 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/512840/	3.74 mg/kg single, oral dose: 3.74 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		QUINIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/512840/	3.74 mg/kg single, oral dose: 3.74 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		QUINIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
8 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/089338s036lbl.pdf	202 mg single, oral dose: 202 mg route of administration: Oral experiment type: SINGLE co-administered:		QUINIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
12% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/089338s036lbl.pdf	202 mg single, oral dose: 202 mg route of administration: Oral experiment type: SINGLE co-administered:		QUINIDINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
200 mg 4 times / day multiple, oral Dose: 200 mg, 4 times / day Route: oral Route: multiple Dose: 200 mg, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1269875	unhealthy, 47 years n = 1 Health Status: unhealthy Age Group: 47 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1269875	Disc. AE: Hepatotoxicity... AEs leading to discontinuation/dose reduction: Hepatotoxicity Sources: https://pubmed.ncbi.nlm.nih.gov/1269875
324 mg 5 times / day multiple, oral Dose: 324 mg, 5 times / day Route: oral Route: multiple Dose: 324 mg, 5 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7604299	unhealthy, 56 yeras n = 1 Health Status: unhealthy Age Group: 56 yeras Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/7604299	Disc. AE: Myalgia... AEs leading to discontinuation/dose reduction: Myalgia (severe, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/7604299
4 g single, oral Overdose Dose: 4 g Route: oral Route: single Dose: 4 g Sources: https://pubmed.ncbi.nlm.nih.gov/5557506	healthy, 57 years n = 1 Health Status: healthy Age Group: 57 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/5557506	Other AEs: Grand mal convulsion, Cardiotoxicity... Other AEs: Grand mal convulsion (1 patient) Cardiotoxicity (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/5557506
324 mg 3 times / day multiple, oral Dose: 324 mg, 3 times / day Route: oral Route: multiple Dose: 324 mg, 3 times / day Co-administed with:: digoxin levothyroxine sodium crystalline warfarin sodium Sources: https://pubmed.ncbi.nlm.nih.gov/7604299	unhealthy, 79 years n = 1 Health Status: unhealthy Age Group: 79 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/7604299	Disc. AE: Drug-induced lupus erythematosus... AEs leading to discontinuation/dose reduction: Drug-induced lupus erythematosus (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/7604299
370 mg 6 times / day multiple, oral Highest studied dose Dose: 370 mg, 6 times / day Route: oral Route: multiple Dose: 370 mg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6747817	healthy, > 23 years n = 1 Health Status: healthy Age Group: > 23 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6747817	Sources: https://pubmed.ncbi.nlm.nih.gov/6747817
1650 mg single, intravenous Dose: 1650 mg Route: intravenous Route: single Dose: 1650 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6747817	healthy, > 23 years n = 1 Health Status: healthy Age Group: > 23 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/6747817	Sources: https://pubmed.ncbi.nlm.nih.gov/6747817

AEs

AE	Significance	Dose	Population
Hepatotoxicity	Disc. AE	200 mg 4 times / day multiple, oral Dose: 200 mg, 4 times / day Route: oral Route: multiple Dose: 200 mg, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1269875	unhealthy, 47 years n = 1 Health Status: unhealthy Age Group: 47 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1269875
Myalgia	severe, 1 patient Disc. AE	324 mg 5 times / day multiple, oral Dose: 324 mg, 5 times / day Route: oral Route: multiple Dose: 324 mg, 5 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7604299	unhealthy, 56 yeras n = 1 Health Status: unhealthy Age Group: 56 yeras Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/7604299
Cardiotoxicity	1 patient	4 g single, oral Overdose Dose: 4 g Route: oral Route: single Dose: 4 g Sources: https://pubmed.ncbi.nlm.nih.gov/5557506	healthy, 57 years n = 1 Health Status: healthy Age Group: 57 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/5557506
Grand mal convulsion	1 patient	4 g single, oral Overdose Dose: 4 g Route: oral Route: single Dose: 4 g Sources: https://pubmed.ncbi.nlm.nih.gov/5557506	healthy, 57 years n = 1 Health Status: healthy Age Group: 57 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/5557506
Drug-induced lupus erythematosus	1 patient Disc. AE	324 mg 3 times / day multiple, oral Dose: 324 mg, 3 times / day Route: oral Route: multiple Dose: 324 mg, 3 times / day Co-administed with:: digoxin levothyroxine sodium crystalline warfarin sodium Sources: https://pubmed.ncbi.nlm.nih.gov/7604299	unhealthy, 79 years n = 1 Health Status: unhealthy Age Group: 79 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/7604299

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1709 inhibitor 1579 inducer 768	substrate 1010 inhibitor 1752	substrate 1193 inhibitor 1837	inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1437 OCT1 506 OCT2 638 OCT3 149 MATE1 304 MATE2 261 CYP1A2 1509 CYP2A6 704 CYP2B6 799 CYP2C8 901 CYP2C19 1463 CYP2E1 876	OCTN1 47 OCTN2 50 P-gp 1527 CYP2E1 648	CYP1A2 689 CYP2B6 538

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1673	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021879s000lbl.pdf#page=14 Page: 14.0	no
CYP1A2 1673	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021879s000lbl.pdf#page=14 Page: 14.0	no
CYP2A6 736	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021879s000lbl.pdf#page=14 Page: 14.0	no
CYP2B6 985	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021879s000lbl.pdf#page=14 Page: 14.0	no
CYP2B6 985	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021879s000lbl.pdf#page=14 Page: 14.0	no
CYP2C19 1537	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021879s000lbl.pdf#page=14 Page: 14.0	no
CYP2C8 955	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021879s000lbl.pdf#page=14 Page: 14.0	no
CYP2C9 1803	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021879s000lbl.pdf#page=14 Page: 14.0	no
CYP2E1 964	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021879s000lbl.pdf#page=14 Page: 14.0	no
CYP3A4 1909	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021879s000lbl.pdf#page=14 Page: 14.0	no
CYP3A4 1909	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021879s000lbl.pdf#page=14 Page: 14.0	no
CYP2D6 1875	inhibitor 3240 Sources: https://www.tandfonline.com/doi/pdf/10.1080/13880209.2016.1223145#page=5; https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/12796s49lbl.pdf#page=2 Page: 5.0	yes [IC50 0.051 uM]	likely (co-administration study) Comment: Caution must be exercixed whenever quinidine is prescribed together with drugs metabolized by CYP2C6. Sources: https://www.tandfonline.com/doi/pdf/10.1080/13880209.2016.1223145#page=5; https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/12796s49lbl.pdf#page=2 Page: 5.0
OCT3 149	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/16141367/	yes [IC50 18.3 uM]
OCT1 523	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/18971316/	yes [IC50 5.7 uM]
OCT2 639	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/16141367/	yes [IC50 8.7 uM]
P-gp 1626	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/12499648/	yes [IC50 9.52 uM]
MATE2 261	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 23.1 uM]
MATE1 306	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/19164462/	yes [Ki 29.2 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2C9 1010	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/10086984/	minor
CYP2D6 1193	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/089338s036lbl.pdf#page=2 Page: 2.0	no
CYP2E1 648	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/10086984/	no
OCTN1 47	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/10215651/	yes
OCTN2 50	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/10525100/	yes
P-gp 1527	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/10628900/ Page: 4.0	yes
CYP3A4 1709	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/089338s036lbl.pdf#page=2 Page: 2.0	yes	likely (co-administration study) Comment: coadministration of quinidine causes variable slowing of the metabolism of nifedipine. Interactions with other dihydropyridine calcium channel blockers have not been reported, but these agents (including felodipine, nicardipine, and nimodipine) are all dependent upon P450IIIA4 for metabolism, so similar interactions with quinidine should be anticipated Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/089338s036lbl.pdf#page=2 Page: 2.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1632	inhibitor 1613 Sources: https://journals.lww.com/cardiovascularpharm/Fulltext/1999/02000/Modulation_of_HERG_Potassium_Channels_by.2.aspx

Sourcing

Vendor/Aggregator	ID	URL
AEchem Scientific Corp., USA	AE020240	http://www.aechemsc.com/info_products/AE020240.php
AK Scientific, Inc. (AKSCI)	6566AF	http://www.aksci.com/item_detail.php?cat=6566AF
AK Scientific, Inc. (AKSCI)	66338	http://www.aksci.com/item_detail.php?cat=66338
Aaron Chemicals	AR003696	http://www.aaronchem.com/56-54-2
AbMole Bioscience	M3406	http://www.abmole.com/products/quinidine.html
Acadechem	ACDS-067325	http://www.acadechemical.com/product/142024
Achemtek	0104-024048	http://www.achemtek.com/56-54-2
Acorn PharmaTech	ACN-052225	http://www.acornpharmatech.com/
Acros Organics	AC163680250	https://www.fishersci.com/shop/products/quinidine-98-anhydrous-acros-organics-1/AC163680250
Acros Organics	AC163681000	https://www.fishersci.com/shop/products/quinidine-98-anhydrous-acros-organics/AC163681000
Alfa Aesar	A12559	https://www.alfa.com/en/catalog/A12559/
Alfa Chemistry	AP56542-A	https://reagents.alfa-chemistry.com/product/quinidine-cas-56-54-2-13236.html
Alfa Chemistry	AP56542-B	https://reagents.alfa-chemistry.com/product/quinidine-cas-56-54-2-13237.html
Alfa Chemistry	ACM56542	https://www.alfachemic.com/catalysts/product/quinidine-cas-56-54-2-180968.html
Alfa Chemistry	56-54-2	https://www.alfachemic.com/catalysts/quinidine-cas-56-54-2-item-180968.htm
Ambinter	Amb17835341	http://www.ambinter.com/reference/17835341
AstaTech, Inc.	23083	http://www.astatechinc.com/CPSResult.php?CRNO=26833
Aurora Fine Chemicals LLC	A24.073.679	http://online.aurorafinechemicals.com/info?ID=A24.073.679
Aurum Pharmatech LLC	M-7594	http://www.Aurumpharmatech.com/Product/ProductDetails/M_7594
Avantor Inc	BT127895-1G	https://us.vwr.com/store/product/16900231/quinidine
Avantor Inc	BT127895-25G	https://us.vwr.com/store/product/16900231/quinidine
Avantor Inc	BT127895-5G	https://us.vwr.com/store/product/16900231/quinidine
BLD Pharm	BD01139139	http://www.bldpharm.com/products/56-54-2.html
BLD Pharm	BD150056	http://www.bldpharm.com/products/56-54-2.html
BLD Pharm	BD01094112	http://www.bldpharm.com/products/66591-62-6.html
BioCrick	BCC7863	http://www.biocrick.com/Quinidine-BCC7863.html
BioSynth	W-109256	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/W-109256.html
CSNpharm	CSN11818	https://www.csnpharm.com/products/quinidine.html
Capot Chemical	7994	http://www.capotchem.com/en/7994.htm
Capot Chemical	PubChem7994	http://www.capotchem.com/en/7994.htm
Chem Scene	CS-7812	http://www.chemscene.com/56-54-2.html
ChemMol	1030683	http://www.chemmol.com/chemmol/1030683.html
ChemMol	99106903	http://www.chemmol.com/chemmol/99106903.html
Chemenu	CM108220	http://www.chemenu.com/products/CM108220
Chemspace	CSSB00016988638	https://chem-space.com/CSSB00016988638
DC Chemicals	DC9066	http://www.dcchemicals.com/product_show-Quinidine.html
Glentham Life Sciences	GE1634	http://www.glentham.com/products/product/GE1634/
Huateng Pharma	F94507	https://en.huatengsci.com/products/intermediates/
LGC Standards	LGCFOR1523.01	https://www.lgcstandards.com/US/en/p/LGCFOR1523.01
LGC Standards	MM1523.01	https://www.lgcstandards.com/US/en/p/MM1523.01
Lab Network	LN00173655	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00173655
Lab Network	LN01747538	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01747538
Matrix Scientific	75925	https://www.matrixscientific.com/075925.html
MedChem Express	HY-B1751	https://www.medchemexpress.com/Quinidine.html
MuseChem	R007506	https://www.musechem.com/product/R007506.html
Oakwood	79244	http://www.oakwoodchemical.com/ProductsList.aspx?CategoryID=-2&txtSearch=64418&ExtHyperLink=1
Parchem	45359	https://www.parchem.com/chemical-supplier-distributor/(1S)-(6-Methoxyquinolin-4-yl)((2R-4S-5R)-5-vinylquinuclidin-2-yl)methanol-045359.aspx
R&D Chemicals	611	http://www.rdchemicals.com/chemicals.php?mode=details&mol_id=8191
Sigma-Aldrich	22600_ALDRICH	https://www.sigmaaldrich.com/catalog/product/aldrich/22600?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	Q3625_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/q3625?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S752224	https://www.smolecule.com/products/s752224
VladaChem	VL144107	https://www.vladachem.com/product.php?products=56-54-2
VladaChem	VL267661-25G	https://www.vladachem.com/product.php?products=56-54-2
VladaChem	VL270184-25G	https://www.vladachem.com/product.php?products=56-54-2
abcr GmbH	AB121200	http://www.abcr.com/shop/en/AB121200
eNovation Chemicals	D378950	http://www.enovationchem.com/productDetails.asp?productID=D378950
eNovation Chemicals	D593773	https://enovationchem.com/ProductDetails.asp?ProductID=D593773
eNovation Chemicals	D674705	https://www.enovationchem.com/ProductDetails.asp?ProductID=D674705
eNovation Chemicals	D766047	https://www.enovationchem.com/ProductDetails.asp?ProductID=D766047
iChemical	EBD2202687	http://www.ichemical.com/products/56-54-2.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
mcule	MCULE-7178915526	https://mcule.com/MCULE-7178915526/

PubMed

Title	Date	PubMed
[Congenital myasthenic syndrome (CMS) caused by postsynaptic defects].	2001	11596412
Is it Crohn's disease? A severe systemic granulomatous reaction to sulfasalazine in patient with rheumatoid arthritis.	2001	11570976
Cytochrome P450 enzymes involved in the metabolic pathway of the histamine 2 (H2)-receptor antagonist roxatidine acetate by human liver microsomes.	2001	11556126
Drug interaction studies with esomeprazole, the (S)-isomer of omeprazole.	2001	11510629
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
Importance of QT interval determination and renal function assessment during antiarrhythmic drug therapy.	2001 Apr	11509917
CIBIS, MERIT-HF, and COPERNICUS trial outcomes: do they complete the chapter on beta-adrenergic blockers as antiarrhythmic and antifibrillatory drugs?	2001 Apr	11509916
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
Study of tea polyphenol as a reversal agent for carcinoma cell lines' multidrug resistance (study of TP as a MDR reversal agent).	2001 Aug	11518657
Independent organic cation transport activity of Na(+)-L-carnitine cotransport system in LLC-PK(1) cells.	2001 Aug	11457718
Identification of cytochrome P-450 isoforms responsible for cis-tramadol metabolism in human liver microsomes.	2001 Aug	11454734
Escitalopram (S-citalopram) and its metabolites in vitro: cytochromes mediating biotransformation, inhibitory effects, and comparison to R-citalopram.	2001 Aug	11454728
Interactions of 1-methyl-4-phenylpyridinium and other compounds with P-glycoprotein: relevance to toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.	2001 Aug 10	11489261
Role of transport proteins in drug absorption, distribution and excretion.	2001 Aug-Sep	11569523
A functional assay for quantitation of the apparent affinities of ligands of P-glycoprotein in Caco-2 cells.	2001 Feb	11405287
Effect of mdr1a P-glycoprotein gene disruption, gender, and substrate concentration on brain uptake of selected compounds.	2001 Jul	11496955
Comparison of "type I" and "type II" organic cation transport by organic cation transporters and organic anion-transporting polypeptides.	2001 Jul	11408531
Cytochrome P450-catalyzed metabolism of ezlopitant alkene (CJ-12,458), a pharmacologically active metabolite of ezlopitant: enzyme kinetics and mechanism of an alkene hydration reaction.	2001 Jul	11408374
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
Novel target genes of the yeast regulator Pdr1p: a contribution of the TPO1 gene in resistance to quinidine and other drugs.	2001 Jul 11	11470516
In vitro evaluation of quinidine sensitivity in Brazilian Plasmodium falciparum isolates: comparative analysis to quinine and chloroquine.	2001 Jul-Aug	11558003
Heterotropic cooperativity of cytochrome P450 3A4 and potential drug-drug interactions.	2001 Jun	11469725
Synchronized neural activity in the Drosophila memory centers and its modulation by amnesiac.	2001 Jun	11430809
Establishment of the transformants expressing human cytochrome P450 subtypes in HepG2, and their applications on drug metabolism and toxicology.	2001 Jun	11377097
Calcium-activated potassium current in single Novikoff cell.	2001 Mar	11484410
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
Oral quinine pharmacokinetics and dietary salt intake.	2001 May	11417441
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
Functional characteristics and steroid hormone-mediated regulation of an organic cation transporter in Madin-Darby canine kidney cells.	2001 Oct	11561104
Interactions of the antimalarial drug mefloquine with the human cardiac potassium channels KvLQT1/minK and HERG.	2001 Oct	11561091
Functional expression of P-glycoprotein in rat brain microglia.	2001 Oct	11561081
In vitro metabolism of tegaserod in human liver and intestine: assessment of drug interactions.	2001 Oct	11560869
Different enantioselective 9-hydroxylation of risperidone by the two human CYP2D6 and CYP3A4 enzymes.	2001 Oct	11560868
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
Development of stereoselective nonaqueous capillary electrophoresis system for the resolution of cationic and amphoteric analytes.	2001 Sep	11589294
Quinidine induced electrocardiographic normalization in two patients with Brugada syndrome.	2001 Sep	11584468
Inactivation of rat cytochrome P450 2D enzyme by a further metabolite of 4-hydroxypropranolol, the major and active metabolite of propranolol.	2001 Sep	11558582
Multidrug resistance-associated protein-1 functional activity in Calu-3 cells.	2001 Sep	11504821
Metabolism of vanoxerine, 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine, by human cytochrome P450 enzymes.	2001 Sep	11502731
Three thiadiazinone derivatives, EMD 60417, EMD 66430, and EMD 66398, with class III antiarrhythmic activity but different electrophysiologic profiles.	2001 Sep	11486248
Purinoreceptors are involved in the control of acute morphine withdrawal.	2001 Sep 21	11669461
Pharmacologic conversion of atrial fibrillation: a systematic review of available evidence.	2001 Sep-Oct	11568824

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: Other

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 `Wed Jul 05 22:47:13 UTC 2023` Edited by `admin` on `Wed Jul 05 22:47:13 UTC 2023`
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

.BETA.-QUINIDINE

Common Name

English

CONQUININE

Common Name

English

QUININE SULFATE IMPURITY A [EP IMPURITY]

Common Name

English

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

Common Name

English

Quinidine [WHO-DD]

Common Name

English

QUININE HYDROCHLORIDE IMPURITY A [EP IMPURITY]

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