QUININE CITRATE

First marketed in 1921

Details

Stereochemistry	ABSOLUTE
Molecular Formula	2C20H24N2O2.C6H8O7
Molecular Weight	840.957
Optical Activity	UNSPECIFIED
Defined Stereocenters	10 / 10
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)CC(O)(CC(O)=O)C(O)=O.[H][C@]1(C[C@@H]2CC[N@]1C[C@@H]2C=C)[C@H](O)C3=C4C=C(OC)C=CC4=NC=C3.[H][C@]5(C[C@@H]6CC[N@]5C[C@@H]6C=C)[C@H](O)C7=C8C=C(OC)C=CC8=NC=C7

InChI

InChIKey=YSFIPRFOHJQXJF-VMJVVOMYSA-N

InChI=1S/2C20H24N2O2.C6H8O7/c2*1-3-13-12-22-9-7-14(13)10-19(22)20(23)16-6-8-21-18-5-4-15(24-2)11-17(16)18;7-3(8)1-6(13,5(11)12)2-4(9)10/h2*3-6,8,11,13-14,19-20,23H,1,7,9-10,12H2,2H3;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)/t2*13-,14-,19-,20+;/m00./s1

HIDE SMILES / InChI

Molecular Formula	C6H8O7
Molecular Weight	192.1235
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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://onlinelibrary.wiley.com/doi/abs/10.1002/jps.3080010617http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021799s024lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.fda.gov/downloads/ForHealthProfessionals/LearningActivities/UCM317816.pdf

QUALAQUIN (quinine sulfate) is an antimalarial drug indicated only for treatment of uncomplicated Plasmodium falciparum malaria. It’s an alkaloid derived from the bark of the cinchona tree and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine sulfate has been shown to be effective in geographical regions where resistance to chloroquine has been documented. Quinine inhibits nucleic acid synthesis, protein synthesis, and glycolysis in Plasmodium falciparum and can bind with hemazoin in parasitized erythrocytes. However, the precise mechanism of the antimalarial activity of quinine sulfate is not completely understood. It is thought to act by inhibiting heme polymerase, thereby allowing accumulation of its cytotoxic substrate, heme. As a schizonticidal drug, it is less effective and more toxic than chloroquine. Quinine is FDA-approved. It is not considered safe and effective for the treatment or prevention of leg cramps-- an "off-label" (non-FDA-approved) use. Quinine is associated with serious and life-threatening adverse events, including: thrombocytopenia, hypersensitivity reactions, and QT prolongation. Thrombocytopenia associated with the use of quinine for the treatment or prevention of leg cramps includes: immune thrombocytopenic purpura, hemolytic uremic syndrome, thrombotic thrombocytepenic purpura with associated renal insufficiency.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Ferriprotoporphyrin IX 43 Target ID: CHEMBL613897 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14967191	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Plasmodium falciparum malaria 63 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021799s024lbl.pdf	Curative		Approved 8429	QUALAQUIN Approved Use is a cinchona alkaloid indicated for treatment of uncomplicated Plasmodium falciparum malaria Launch Date 2005

C_max

Value	Dose	Co-administered	Analyte	Population
3.2 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021799s029lbl.pdf	8.7 mg/kg single, oral dose: 8.7 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		QUININE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
28 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021799s029lbl.pdf	8.7 mg/kg single, oral dose: 8.7 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		QUININE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
12.5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021799s029lbl.pdf	8.7 mg/kg single, oral dose: 8.7 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		QUININE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
8% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021799s029lbl.pdf	8.7 mg/kg single, oral dose: 8.7 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		QUININE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
5 g single, oral Dose: 5 g Route: oral Route: single Dose: 5 g Sources: https://pubmed.ncbi.nlm.nih.gov/2566088	unhealthy, 17 years n = 1 Health Status: unhealthy Age Group: 17 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/2566088	Other AEs: Respiratory distress... Other AEs: Respiratory distress (grade 5, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/2566088
1.8 g single, oral Overdose Dose: 1.8 g Route: oral Route: single Dose: 1.8 g Sources: https://pubmed.ncbi.nlm.nih.gov/28778932	unhealthy, 46 years n = 1 Health Status: unhealthy Age Group: 46 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/28778932	Other AEs: Hearing loss... Other AEs: Hearing loss (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/28778932
16250 mg single, oral Overdose Dose: 16250 mg Route: oral Route: single Dose: 16250 mg Sources: https://pubmed.ncbi.nlm.nih.gov/8340583	unhealthy, 49 years n = 1 Health Status: unhealthy Age Group: 49 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/8340583	Other AEs: Cardiotoxicity... Other AEs: Cardiotoxicity (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/8340583
9.75 g single, oral Dose: 9.75 g Route: oral Route: single Dose: 9.75 g Sources: https://pubmed.ncbi.nlm.nih.gov/14640479	unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/14640479	Other AEs: Tachycardia... Other AEs: Tachycardia (grade 5) Sources: https://pubmed.ncbi.nlm.nih.gov/14640479

AEs

AE	Significance	Dose	Population
Respiratory distress	grade 5, 1 patient	5 g single, oral Dose: 5 g Route: oral Route: single Dose: 5 g Sources: https://pubmed.ncbi.nlm.nih.gov/2566088	unhealthy, 17 years n = 1 Health Status: unhealthy Age Group: 17 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/2566088
Hearing loss	1 patient	1.8 g single, oral Overdose Dose: 1.8 g Route: oral Route: single Dose: 1.8 g Sources: https://pubmed.ncbi.nlm.nih.gov/28778932	unhealthy, 46 years n = 1 Health Status: unhealthy Age Group: 46 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/28778932
Cardiotoxicity	1 patient	16250 mg single, oral Overdose Dose: 16250 mg Route: oral Route: single Dose: 16250 mg Sources: https://pubmed.ncbi.nlm.nih.gov/8340583	unhealthy, 49 years n = 1 Health Status: unhealthy Age Group: 49 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/8340583
Tachycardia	grade 5	9.75 g single, oral Dose: 9.75 g Route: oral Route: single Dose: 9.75 g Sources: https://pubmed.ncbi.nlm.nih.gov/14640479	unhealthy, adult n = 1 Health Status: unhealthy Age Group: adult Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/14640479

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:15854	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:15854
MolPort	MolPort-000-146-082	https://www.molport.com/shop/molecule-link/MolPort-000-146-082
ZINC	ZINC000003831404	http://zinc15.docking.org/substances/ZINC000003831404
eMolecules	29549573	https://www.emolecules.com/cgi-bin/more?vid=29549573
eMolecules	30151887	https://www.emolecules.com/cgi-bin/more?vid=30151887
eMolecules	6843708	https://www.emolecules.com/cgi-bin/more?vid=6843708

PubMed

Title	Date	PubMed
Quinine-induced alterations of electrically evoked otoacoustic emissions and cochlear potentials in guinea pigs.	2001 Apr	11423223
Two procedures establishing preference for oral cocaine and lidocaine solutions which do not use an associative history with a reinforcer.	2001 Apr	11396516
The first stereoselective total synthesis of quinine.	2001 Apr 11	11457058
Role of parabrachial nucleus in submandibular salivary secretion induced by bitter taste stimulation in rats.	2001 Apr 12	11474548
Simultaneous determination of quinine and four metabolites in plasma and urine by high-performance liquid chromatography.	2001 Apr 15	11318427
Resurgence of blackwater fever in long-term European expatriates in Africa: report of 21 cases and review.	2001 Apr 15	11283802
Soa genotype selectively affects mouse gustatory neural responses to sucrose octaacetate.	2001 Apr 27	11328963
Quinine-induced thrombocytopenia in a 64-year-old man who consumed tonic water to relieve nocturnal leg cramps.	2001 Aug	11499830
5-HT1A receptor-mediated activation of G-protein-gated inwardly rectifying K+ current in rat periaqueductal gray neurons.	2001 Aug	11489454
Ferrocene-chloroquine analogues as antimalarial agents: in vitro activity of ferrochloroquine against 103 Gabonese isolates of Plasmodium falciparum.	2001 Aug	11481286
Role of quinine-sensitive ion channels in volume regulation in boar and bull spermatozoa.	2001 Aug	11467984
Determination of cisapride in pharmaceutical preparations using derivative spectrophotometry.	2001 Feb	11272323
In vitro antiplasmodial activity of 4-phenylcoumarins from Exostema mexicanum.	2001 Feb	11270733
The applicability of rat and human liver slices to the study of mechanisms of hepatic drug uptake.	2001 Jan-Feb	11489665
Evaluation under field conditions of the colourimetric DELI-microtest for the assessment of Plasmodium falciparum drug resistance.	2001 Jan-Feb	11280052
[Effect of antibodies against S100 proteins on neural plasticity in sensitized and naive snails].	2001 Jan-Feb	11253403
Effectiveness of short-course quinine and single-dose sulfadoxine-pyrimethamine in the treatment of Plasmodium falciparum malaria in Mpumalanga Province, South Africa.	2001 Jul	11544977
Covariation in individuals' sensitivities to bitter compounds: evidence supporting multiple receptor/transduction mechanisms.	2001 Jul	11521845
Apparent drug failure following artesunate treatment of Plasmodium falciparum malaria in Freetown, Sierra Leone: four case reports.	2001 Jul	11487367
Apoptosis induced by doxorubicin and cinchonine in P388 multidrug-resistant cells.	2001 Jul	11480538
Simultaneous determination of etoposide and its catechol metabolite in the plasma of pediatric patients by liquid chromatography/tandem mass spectrometry.	2001 Jul	11473400
Sapid solutions and food intake in repeated dehydration and rehydration periods in rats.	2001 Jul	11445828
Polyvinyl chloride-based membranes for flow injection analysis of quinine in beverages.	2001 Jul-Aug	11501917
Myosin II-dependent cylindrical protrusions induced by quinine in Dictyostelium: antagonizing effects of actin polymerization at the leading edge.	2001 Jun	11493651
Lateral parabrachial nucleus lesions in the rat: neophobia and conditioned taste aversion.	2001 Jun	11489343
The effect of laser assisted uvulopalatoplasty on the sense of smell and taste.	2001 Jun	11486433
Therapeutic efficacy of sulphadoxine/pyrimethamine and susceptibility in vitro of P. falciparum isolates to sulphadoxine-pyremethamine and other antimalarial drugs in Malawian children.	2001 Jun	11422956
Transfusion-transmitted babesiosis in Ontario: first reported case in Canada.	2001 Jun 12	11450217
Dynamic and multimodal responses of gustatory cortical neurons in awake rats.	2001 Jun 15	11404435
Mechanisms by which intracellular calcium induces susceptibility to secretory phospholipase A2 in human erythrocytes.	2001 Jun 22	11294854
[Photodermatosis induced by hydroxychloroquine: 4 cases].	2001 Jun-Jul	11460035
Effects of hydroxypyridinone iron chelators in combination with antimalarial drugs on the in vitro growth of Plasmodium falciparum.	2001 Mar	11485097
Persistence of Plasmodium falciparum in the placenta after apparently effective quinidine/clindamycin therapy.	2001 Mar	11324359
Genomic and functional characteristics of novel human pancreatic 2P domain K(+) channels.	2001 Mar 23	11263999
Changes in taste intensity perception following anterior temporal lobe removal in humans.	2001 May	11369677
Effect of compound sequence on bitterness enhancement.	2001 May	11369676
Interaction of gustatory and lingual somatosensory perceptions at the cortical level in the human: a functional magnetic resonance imaging study.	2001 May	11369672
Molecular cloning and characterization of a novel (Na+,K+)/H+ exchanger localized to the trans-Golgi network.	2001 May 18	11279194
Resistance of Plasmodium falciparum to antimalarial drugs in a highly endemic area of southern Viet Nam: a study in vivo and in vitro.	2001 May-Jun	11491008
A clinical and pharmacokinetic trial of six doses of artemether-lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand.	2001 May-Jun	11463111
Clinical trial of beta-arteether versus quinine for the treatment of cerebral malaria in children in Yaounde, Cameroon.	2001 May-Jun	11463108
Effects of the ion-channel blocker quinine on human sperm volume, kinematics and mucus penetration, and the involvement of potassium channels.	2001 Sep	11517288
Is multiple sclerosis caused by a silent infection with malarial parasites? A historico-epidemiological approach: part II.	2001 Sep	11516219
Volume-activated trimethylamine oxide efflux in red blood cells of spiny dogfish (Squalus acanthias).	2001 Sep	11506995
Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1.	2001 Sep	11502595
Antimalarial activity of azithromycin, artemisinin and dihydroartemisinin in fresh isolates of Plasmodium falciparum in Thailand.	2001 Sep 1	11495642
Septic shock due to babesiosis.	2001 Sep 1	11477535
Optochin resistance in Streptococcus pneumoniae: mechanism, significance, and clinical implications.	2001 Sep 1	11474432
HPLC of basic drugs on microparticulate strong cation-exchange materials - a review.	2001 Sep 15	11516893
Properties and regulation of organic cation transport in freshly isolated human proximal tubules.	2001 Sep 7	11447227

Patents

Sample Use Guides

In Vivo Use Guide

in adults: 648 mg (two capsules) every 8 hours for 7 days

Route of Administration: Oral

In Vitro Use Guide

Quinine (0-100 uM) stimulates adipogenesis through ERK/S6 (extracellular-signal-regulated kinase/Ribosomal protein S6) signaling, which at least partly functions via taste receptor, type 2, member 106 (T2R106)

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:13:57 GMT 2023` Edited by `admin` on `Fri Dec 15 15:13:57 GMT 2023`
Record UNII	L8D5LFU229
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

QUININE CITRATE

Common Name

English

Quinine citrate [WHO-DD]

Common Name

English

QUININE, CITRATE (2:1) (SALT)

Common Name

English

CINCHONAN-9-OL, 6'-METHOXY-, (8.ALPHA.,9R)-, 2-HYDROXY-1,2,3-PROPANETRICARBOXYLATE (2:1) (SALT)

Common Name

English

Classification Tree Code System Code

CFR

21 CFR 310.547