QUININE BISULFATE HEPTAHYDRATE

First marketed in 1921

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H24N2O2.7H2O.H2O4S
Molecular Weight	548.602
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of QUININE BISULFATE HEPTAHYDRATE

Structure Search

SMILES

O.O.O.O.O.O.O.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=MMZACAMEMISONC-RYXXBYBMSA-N

InChI=1S/C20H24N2O2.H2O4S.7H2O/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);7*1H2/t13-,14-,19-,20+;;;;;;;;/m0......../s1

HIDE SMILES / InChI

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
Drug-induced thrombotic microangiopathy: incidence, prevention and management.	2001	11444722
Quinine-induced alterations of electrically evoked otoacoustic emissions and cochlear potentials in guinea pigs.	2001 Apr	11423223
Cell volume-induced changes in K+ transport across the rat colon.	2001 Apr	11421860
Two procedures establishing preference for oral cocaine and lidocaine solutions which do not use an associative history with a reinforcer.	2001 Apr	11396516
HPTLC method for the estimation of alkaloids of Cinchona officinalis stem bark and its marketed formulations.	2001 Apr	11345710
Use of the DELI-microtest to determine the drug sensitivity of Plasmodium falciparum in Burkina Faso.	2001 Apr	11339890
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
[Plasmodium vivax: therapy update].	2001 Apr 21	11360746
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
Large-conductance calcium-activated potassium channels in neonatal rat intracardiac ganglion neurons.	2001 Feb	11294244
Stereocontrolled conversion of quinine into 10(R),11-dihydroxydihydroquinine via the sharpless osmylation process.	2001 Feb 23	11312991
The applicability of rat and human liver slices to the study of mechanisms of hepatic drug uptake.	2001 Jan-Feb	11489665
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
A comparison of the in vivo kinetics of Plasmodium falciparum ring-infected erythrocyte surface antigen-positive and -negative erythrocytes.	2001 Jul 15	11435316
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
Influence of quinine on catecholamine release evoked by cholinergic stimulation and membrane depolarization from the rat adrenal gland.	2001 Jun	11440085
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
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
[Treatment of acute malaria with quinine in a non-immunized patient: rationale for a 7-day regimen].	2001 Mar 17	11307490
Oral quinine pharmacokinetics and dietary salt intake.	2001 May	11417441
Effect of compound sequence on bitterness enhancement.	2001 May	11369676
Treatment alternatives for nocturnal leg cramps.	2001 May 21	11419779
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
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)

Name

Type

Language

QUININE BISULFATE HEPTAHYDRATE

Common Name

English

Quinine bisulfate heptahydrate [WHO-DD]

Common Name

English

CINCHONAN-9-OL, 6'-METHOXY-, (8.ALPHA.,9R)-, SULFATE, HYDRATE (1:1:7)

Systematic Name

English

QUININI BISULFAS [WHO-IP LATIN]

Common Name

English

QUININE BISULFATE [WHO-IP]

Common Name

English

QUININE BISULPHATE HEPTAHYDRATE

Common Name

English

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

Common Name

English

QUININE BISULFATE [MART.]

Common Name

English

QUININE BISULFATE HEPTAHYDRATE [MI]

Common Name

English

QUININE SULFATE (1:1) (SALT), HEPTAHYDRATE [WHO-IP]

Common Name

English

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

Common Name

English

BIQUINATE

Brand Name

English

Classification Tree Code System Code

CFR

21 CFR 310.547