QUININE ETHYLCARBONATE

First marketed in 1921

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H28N2O4
Molecular Weight	396.4794
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](OC(=O)OCC)C3=C4C=C(OC)C=CC4=NC=C3

InChI

InChIKey=NSBRKSWSLRQPJW-WWLNLUSPSA-N

InChI=1S/C23H28N2O4/c1-4-15-14-25-11-9-16(15)12-21(25)22(29-23(26)28-5-2)18-8-10-24-20-7-6-17(27-3)13-19(18)20/h4,6-8,10,13,15-16,21-22H,1,5,9,11-12,14H2,2-3H3/t15-,16-,21-,22+/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
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
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
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
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
Severe babesiosis in Long Island: review of 34 cases and their complications.	2001 Apr 15	11283800
[Plasmodium vivax: therapy update].	2001 Apr 21	11360746
Soa genotype selectively affects mouse gustatory neural responses to sucrose octaacetate.	2001 Apr 27	11328963
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
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
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
Distribution of gustatory sensitivities in rat taste cells: whole-cell responses to apical chemical stimulation.	2001 Jul 1	11425921
A comparison of the in vivo kinetics of Plasmodium falciparum ring-infected erythrocyte surface antigen-positive and -negative erythrocytes.	2001 Jul 15	11435316
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
A comparison of brain, core and skin temperature in children with complicated and uncomplicated malaria.	2001 Jun	11419682
Nocturnal leg cramps. Clinically mysterious and painful--but manageable.	2001 Jun	11417373
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
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
Genomic and functional characteristics of novel human pancreatic 2P domain K(+) channels.	2001 Mar 23	11263999
[Severe malaria].	2001 Mar 31	11345866
Exchange transfusion for severe malaria.	2001 Mar-Apr	11339483
Oral quinine pharmacokinetics and dietary salt intake.	2001 May	11417441
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
Treatment alternatives for nocturnal leg cramps.	2001 May 21	11419779
Chemistry. Synthetic lessons from quinine.	2001 May 24	11373659
Evaluation of the contribution to enantioselectivity of quinine and quinidine scaffolds in chemically and physically mixed chiral selectors.	2001 May 5	11284022
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
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

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 ETHYLCARBONATE

Common Name

English

QUININE ETABONATE [MART.]

Common Name

English

QUININE ETABONATE

Common Name

English

EUQUININE

Common Name

English

QUININE ETHYLCARBONATE [JAN]

Common Name

English

QUININE ETHYL CARBONATE

Common Name

English

NSC-755879

Code

English

AECACHINIUM

Common Name

English

Quinine ethylcarbonate [WHO-DD]

Common Name

English

EUQUININ

Common Name

English

CINCHONAN-9-OL, 6'-METHOXY-, 9-(ETHYL CARBONATE), (8.ALPHA.,9R)-

Common Name

English

Code System Code Type Description

NSC

755879