QUININE HYDROCHLORIDE ANHYDROUS

First marketed in 1921

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H24N2O2.ClH
Molecular Weight	360.878
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of QUININE HYDROCHLORIDE ANHYDROUS

Structure Search

SMILES

Cl.[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=LBSFSRMTJJPTCW-DSXUQNDKSA-N

InChI=1S/C20H24N2O2.ClH/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;/h3-6,8,11,13-14,19-20,23H,1,7,9-10,12H2,2H3;1H/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
Olfactory learning induces differential long-lasting changes in rat central olfactory pathways.	2001	11226666
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
Use of the DELI-microtest to determine the drug sensitivity of Plasmodium falciparum in Burkina Faso.	2001 Apr	11339890
Muscimol infusions in the brain stem reticular formation reversibly block ingestion in the awake rat.	2001 Apr	11247831
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
Severe babesiosis in Long Island: review of 34 cases and their complications.	2001 Apr 15	11283800
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
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
Reduction of saltiness and bitterness after a chlorhexidine rinse.	2001 Feb	11238242
Delayed quinine toxicity mimicking open angle glaucoma.	2001 Feb	11225580
Computer-simulation studies on roles of potassium currents in neurotransmission of the auditory nerve.	2001 Feb	11223284
Activation of ion-conducting pathways in the inner mitochondrial membrane - an unrecognized activity of fatty acid?	2001 Feb 23	11226416
Taste receptor cells that discriminate between bitter stimuli.	2001 Feb 23	11222863
Ethanol perception and ingestion.	2001 Jan	11240000
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
[Fulminant course of falciparum malaria].	2001 Jan 26	11218564
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
Sapid solutions and food intake in repeated dehydration and rehydration periods in rats.	2001 Jul	11445828
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
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
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
[Severe malaria].	2001 Mar 31	11345866
The treatment of babesiosis.	2001 Mar 8	11236790
Characterization of TASK-4, a novel member of the pH-sensitive, two-pore domain potassium channel family.	2001 Mar 9	11248242
Exchange transfusion for severe malaria.	2001 Mar-Apr	11339483
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
Antimalarial activity of azithromycin, artemisinin and dihydroartemisinin in fresh isolates of Plasmodium falciparum in Thailand.	2001 Sep 1	11495642
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 HYDROCHLORIDE ANHYDROUS

Common Name

English

QUININE HYDROCHLORIDE [FHFI]

Common Name

English

Quinine hydrochloride [WHO-DD]

Common Name

English

ANHYDROUS QUININE HYDROCHLORIDE

Common Name

English

QUININE MURIATE

Common Name

English

QUININE HYDROCHLORIDE ANHYDROUS [MI]

Common Name

English

FEMA NO. 2976

Code

English

(8.ALPHA.,9R)-6'-METHOXYCINCHONAN-9-OL HYDROCHLORIDE

Common Name

English

QUININE MONOHYDROCHLORIDE ANHYDROUS

Common Name

English

Classification Tree Code System Code

CFR

21 CFR 310.547