QUININE BISULFATE

First marketed in 1921

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H24N2O2.H2O4S
Molecular Weight	422.495
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OS(O)(=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

InChI

InChIKey=AKYHKWQPZHDOBW-DSXUQNDKSA-N

InChI=1S/C20H24N2O2.H2O4S/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;1-5(2,3)4/h3-6,8,11,13-14,19-20,23H,1,7,9-10,12H2,2H3;(H2,1,2,3,4)/t13-,14-,19-,20+;/m0./s1

HIDE SMILES / InChI

Molecular Formula	H2O4S
Molecular Weight	98.078
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
The effect of artesunate combined with standard antimalarials against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum in vitro.	1999 Jul-Aug	10674097
Drug-induced thrombotic microangiopathy: incidence, prevention and management.	2001	11444722
Patterns of Plasmodium falciparum drug resistance in nonimmune travellers to Africa.	2001 Apr	11399022
Simultaneous separation of the stereoisomers of 1-amino-2-hydroxy and 2-amino-1-hydroxypropane phosphonic acids by stereoselective capillary electrophoresis employing a quinine carbamate type chiral selector.	2001 Apr	11358145
HPTLC method for the estimation of alkaloids of Cinchona officinalis stem bark and its marketed formulations.	2001 Apr	11345710
Resurgence of blackwater fever in long-term European expatriates in Africa: report of 21 cases and review.	2001 Apr 15	11283802
Severe babesiosis in Long Island: review of 34 cases and their complications.	2001 Apr 15	11283800
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
Role of quinine-sensitive ion channels in volume regulation in boar and bull spermatozoa.	2001 Aug	11467984
Large-conductance calcium-activated potassium channels in neonatal rat intracardiac ganglion neurons.	2001 Feb	11294244
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
BK channels in human glioma cells.	2001 Feb	11160513
Stereocontrolled conversion of quinine into 10(R),11-dihydroxydihydroquinine via the sharpless osmylation process.	2001 Feb 23	11312991
Taste receptor cells that discriminate between bitter stimuli.	2001 Feb 23	11222863
Characterization of an intense bitter-tasting 1H,4H-quinolizinium-7-olate by application of the taste dilution analysis, a novel bioassay for the screening and identification of taste-active compounds in foods.	2001 Jan	11170582
Comparative expression of hedonic impact: affective reactions to taste by human infants and other primates.	2001 Jan	11166078
Redox systems as conduits for antimalarial compounds.	2001 Jan	11152448
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
Cellular responses of NG108-15 and SK-N-MC lines to sweet and bitter tastants as measured by extracellular acidification rates.	2001 Jan 1	11169615
Declining chloroquine resistance of Plasmodium falciparum in Lambaréné, Gabon from 1992 to 1998.	2001 Jan 15	11233471
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
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
Distribution of gustatory sensitivities in rat taste cells: whole-cell responses to apical chemical stimulation.	2001 Jul 1	11425921
Polyvinyl chloride-based membranes for flow injection analysis of quinine in beverages.	2001 Jul-Aug	11501917
Transfusion-transmitted babesiosis in Ontario: first reported case in Canada.	2001 Jun 12	11450217
Mechanisms by which intracellular calcium induces susceptibility to secretory phospholipase A2 in human erythrocytes.	2001 Jun 22	11294854
Effects of hydroxypyridinone iron chelators in combination with antimalarial drugs on the in vitro growth of Plasmodium falciparum.	2001 Mar	11485097
Capillary electrophoretic separation, immunochemical recognition and analysis of the diastereomers quinine and quinidine and two quinidine metabolites in body fluids.	2001 Mar	11248471
[Treatment of acute malaria with quinine in a non-immunized patient: rationale for a 7-day regimen].	2001 Mar 17	11307490
Genomic and functional characteristics of novel human pancreatic 2P domain K(+) channels.	2001 Mar 23	11263999
Characterization of TASK-4, a novel member of the pH-sensitive, two-pore domain potassium channel family.	2001 Mar 9	11248242
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
A clinical and pharmacokinetic trial of six doses of artemether-lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand.	2001 May-Jun	11463111
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
Septic shock due to babesiosis.	2001 Sep 1	11477535
HPLC of basic drugs on microparticulate strong cation-exchange materials - a review.	2001 Sep 15	11516893

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 `Sat Dec 16 00:23:30 GMT 2023` Edited by `admin` on `Sat Dec 16 00:23:30 GMT 2023`
Record UNII	M201HC068W
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

QUININE BISULFATE

Common Name

English

QUININE, SULFATE (1:1) (SALT)

Common Name

English

QUININE BISULFATE ANHYDROUS [MI]

Common Name

English

Quinine bisulfate [WHO-DD]

Common Name

English

QUININE HYDROGEN SULFATE

Common Name

English

ANHYDROUS QUININE BISULFATE

Common Name

English

QUININE BISULFATE [FHFI]

Common Name

English

ANHYDROUS QUININE BISULFATE [MART.]

Common Name

English

CINCHONAN-9-OL, 6'-METHOXY-, (8.ALPHA.,9R)-, SULFATE (1:1)

Common Name

English

FEMA NO. 2975

Code

English

CINCHONAN-9-OL, 6'-METHOXY-, (8.ALPHA.,9R)-, SULFATE (1:1) (SALT)

Common Name

English

Classification Tree Code System Code

CFR

21 CFR 310.547