QUININE SULFATE

First marketed in 1921

Details

Stereochemistry	ABSOLUTE
Molecular Formula	2C20H24N2O2.2H2O.H2O4S
Molecular Weight	782.943
Optical Activity	UNSPECIFIED
Defined Stereocenters	10 / 10
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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.[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=ZHNFLHYOFXQIOW-LPYZJUEESA-N

InChI=1S/2C20H24N2O2.H2O4S.2H2O/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;1-5(2,3)4;;/h2*3-6,8,11,13-14,19-20,23H,1,7,9-10,12H2,2H3;(H2,1,2,3,4);2*1H2/t2*13-,14-,19-,20+;;;/m00.../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
Patterns of Plasmodium falciparum drug resistance in nonimmune travellers to Africa.	2001 Apr	11399022
Two procedures establishing preference for oral cocaine and lidocaine solutions which do not use an associative history with a reinforcer.	2001 Apr	11396516
Muscimol infusions in the brain stem reticular formation reversibly block ingestion in the awake rat.	2001 Apr	11247831
The first stereoselective total synthesis of quinine.	2001 Apr 11	11457058
Soa genotype selectively affects mouse gustatory neural responses to sucrose octaacetate.	2001 Apr 27	11328963
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
Reduction of saltiness and bitterness after a chlorhexidine rinse.	2001 Feb	11238242
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
Redox systems as conduits for antimalarial compounds.	2001 Jan	11152448
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
Effect of extracellular Ca2+ on the quinine-activated current of bullfrog taste receptor cells.	2001 Jan 15	11208971
The applicability of rat and human liver slices to the study of mechanisms of hepatic drug uptake.	2001 Jan-Feb	11489665
Simultaneous determination of etoposide and its catechol metabolite in the plasma of pediatric patients by liquid chromatography/tandem mass spectrometry.	2001 Jul	11473400
A comparison of the in vivo kinetics of Plasmodium falciparum ring-infected erythrocyte surface antigen-positive and -negative erythrocytes.	2001 Jul 15	11435316
Myosin II-dependent cylindrical protrusions induced by quinine in Dictyostelium: antagonizing effects of actin polymerization at the leading edge.	2001 Jun	11493651
Dynamic and multimodal responses of gustatory cortical neurons in awake rats.	2001 Jun 15	11404435
[Photodermatosis induced by hydroxychloroquine: 4 cases].	2001 Jun-Jul	11460035
[Severe malaria].	2001 Mar 31	11345866
The treatment of babesiosis.	2001 Mar 8	11236790
Hyperpolarizing shift by quinine in the steady-state inactivation curve of delayed rectifier-type potassium current in bullfrog sympathetic neurons.	2001 Mar 9	11207381
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
Chemistry. Synthetic lessons from quinine.	2001 May 24	11373659
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
Volume-activated trimethylamine oxide efflux in red blood cells of spiny dogfish (Squalus acanthias).	2001 Sep	11506995
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 SULFATE

Common Name

English

QUININE SULFATE HYDRATE

Common Name

English

QUININE SULFATE DIHYDRATE [MART.]

Common Name

English

QUININE SULFATE [VANDF]

Common Name

English

FEMA NO. 2977

Code

English

QUININE SULPHATE [WHO-IP]

Common Name

English

GLS 1200 [WHO-DD]

Common Name

English

CHININUM SULPHURICUM

Common Name

English

QUININE SULFATE [FHFI]

Common Name

English

QUININE SULFATE [FCC]

Common Name

English

Quinine sulfate (2:1) (salt) dihydrate

Systematic Name

English

GLS-1200

Code

English

QUININE SULFATE [MART.]

Common Name

English

QUININE SULPHATE

Common Name

English

NSC-757298

Code

English

QUINATE

Brand Name

English

QUININE SULFATE [EP MONOGRAPH]

Common Name

English

QUININE SULFATE [USP-RS]

Common Name

English

QUININE SULFATE DIHYDRATE [MI]

Common Name

English

QUININE SULFATE HYDRATE [JAN]

Common Name

English

QUININE SULFATE [USP IMPURITY]

Common Name

English

CINCHONAN-9-OL, 6'-METHOXY-, (8.ALPHA.,9R)-, SULFATE, HYDRATE (2:1:2)

Common Name

English

CHININUM SULPHURICUM [HPUS]

Common Name

English

QUININE SULFATE DIHYDRATE

Common Name

English

QUINAMM

Brand Name

English

QUININE SULFATE [USP MONOGRAPH]

Common Name

English

GLS1200

Code

English

QUININE SULFATE [ORANGE BOOK]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C271