quinine Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
	4523	130-95-0

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: quinine bisulfate heptahydrate chinine qualaquin quinine quinine sulfate	An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. Molecular weight: 324.42 Formula: C20H24N2O2 CLOGP: 2.79 LIPINSKI: 0 HAC: 4 HDO: 1 TPSA: 45.59 ALOGS: -2.99 ROTB: 4 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

quinine bisulfate heptahydrate
chinine
qualaquin
quinine
quinine sulfate

An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood.

Molecular weight: 324.42
Formula: C20H24N2O2
CLOGP: 2.79
LIPINSKI: 0
HAC: 4
HDO: 1
TPSA: 45.59
ALOGS: -2.99
ROTB: 4

Status: OFP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
1.50	g	O
1.50	g	P

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	111.10 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	12 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	71.07 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution)	1.80 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	1.90 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.30 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	11 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Aug. 12, 2005	FDA	MUTUAL PHARM CO INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Drug abuse	189.73	13.39	144	11579	63264	46611075
Labile blood pressure	119.65	13.39	35	11688	1668	46672671
Sacroiliitis	90.85	13.39	30	11693	2139	46672200
Somatic symptom disorder	90.45	13.39	29	11694	1883	46672456
Haematemesis	57.89	13.39	52	11671	28754	46645585
Hepatic ischaemia	47.30	13.39	13	11710	493	46673846
Coronary artery disease	47.29	13.39	50	11673	33702	46640637
Hepatorenal syndrome	45.06	13.39	17	11706	1791	46672548
Hepatic failure	44.17	13.39	48	11675	33368	46640971
Thrombotic microangiopathy	41.71	13.39	26	11697	8280	46666059
Muscle relaxant therapy	41.68	13.39	9	11714	120	46674219
Electrocardiogram QT prolonged	39.24	13.39	56	11667	51269	46623070
Renal failure	38.69	13.39	87	11636	113507	46560832
Lipase increased	38.40	13.39	25	11698	8578	46665761
Mood altered	37.62	13.39	29	11694	12978	46661361
Fear of eating	37.44	13.39	10	11713	340	46673999
Duodenal ulcer	37.27	13.39	23	11700	7195	46667144
Hyponatraemia	34.94	13.39	78	11645	101254	46573085
Rheumatoid arthritis	34.31	13.39	9	11714	240206	46434133
Drug ineffective	32.51	13.39	77	11646	677761	45996578
Plasmodium falciparum infection	30.68	13.39	6	11717	47	46674292
Coagulopathy	30.63	13.39	30	11693	18469	46655870
Retinal toxicity	30.08	13.39	11	11712	1062	46673277
Off label use	29.72	13.39	31	11692	379810	46294529
Product dose omission issue	28.94	13.39	4	11719	168516	46505823
Drug hypersensitivity	27.07	13.39	127	11596	243698	46430641
Cinchonism	26.39	13.39	4	11719	4	46674335
Swollen tongue	25.49	13.39	34	11689	29198	46645141
Vascular injury	24.95	13.39	9	11714	835	46673504
Blood sodium decreased	24.93	13.39	29	11694	21697	46652642
Toxicity to various agents	24.75	13.39	112	11611	211654	46462685
Vestibular disorder	24.07	13.39	10	11713	1356	46672983
Rhabdomyolysis	23.97	13.39	40	11683	41869	46632470
Optic ischaemic neuropathy	23.80	13.39	9	11714	954	46673385
Purpura senile	23.49	13.39	8	11715	627	46673712
Fatigue	23.30	13.39	77	11646	608620	46065719
Tarsal tunnel syndrome	23.24	13.39	8	11715	647	46673692
Salivary gland enlargement	23.09	13.39	7	11716	377	46673962
Oral cavity fistula	22.48	13.39	8	11715	714	46673625
Fibromyalgia	22.48	13.39	36	11687	36427	46637912
Hypovolaemia	22.16	13.39	19	11704	9869	46664470
Myocardial ischaemia	21.72	13.39	21	11702	12728	46661611
Exostosis of jaw	21.62	13.39	9	11714	1227	46673112
Muscle necrosis	20.45	13.39	7	11716	557	46673782
Eczema asteatotic	20.44	13.39	6	11717	289	46674050
Cerebral artery occlusion	20.31	13.39	8	11715	946	46673393
Abdominal rigidity	19.27	13.39	9	11714	1613	46672726
Resorption bone increased	19.02	13.39	8	11715	1119	46673220
Gastrointestinal haemorrhage	18.67	13.39	52	11671	77321	46597018
Exposed bone in jaw	18.57	13.39	11	11712	3197	46671142
Haemolytic uraemic syndrome	18.26	13.39	10	11713	2504	46671835
Cognitive disorder	18.22	13.39	33	11690	36850	46637489
Acute kidney injury	18.07	13.39	111	11612	235744	46438595
Adrenal mass	17.72	13.39	7	11716	834	46673505
Injection site pain	17.35	13.39	3	11720	107149	46567190
Drug intolerance	16.73	13.39	8	11715	147041	46527298
Coronary artery bypass	15.78	13.39	9	11714	2436	46671903
Agitated depression	15.12	13.39	4	11719	131	46674208
Completed suicide	15.04	13.39	9	11714	145911	46528428
Rectal haemorrhage	14.95	13.39	31	11692	38224	46636115
Gastritis	14.79	13.39	29	11694	34349	46639990
Confusional state	14.69	13.39	79	11644	159813	46514526
Somnambulism	14.06	13.39	11	11712	5026	46669313
Infusion related reaction	14.04	13.39	4	11719	101204	46573135
Fall	14.02	13.39	135	11588	328962	46345377
Bradycardia	13.54	13.39	42	11681	66256	46608083
Pharyngeal hypoaesthesia	13.43	13.39	4	11719	203	46674136

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Drug abuse	1039.00	17.69	461	6527	81611	29863879
Toxicity to various agents	222.77	17.69	238	6750	176945	29768545
Poisoning	85.14	17.69	45	6943	11337	29934153
Intentional product misuse	54.87	17.69	53	6935	34614	29910876
Exposure via ingestion	53.98	17.69	21	6967	2590	29942900
Compartment syndrome	47.60	17.69	19	6969	2508	29942982
Electrocardiogram U wave present	42.37	17.69	7	6981	19	29945471
Atrioventricular block	36.07	17.69	22	6966	7260	29938230
Cinchonism	33.88	17.69	5	6983	4	29945486
Muscle spasms	33.87	17.69	57	6931	64781	29880709
Hypomagnesaemia	33.31	17.69	29	6959	16569	29928921
Mouth swelling	30.03	17.69	12	6976	1587	29943903
Urine sodium decreased	28.41	17.69	7	6981	185	29945305
Agitated depression	26.83	17.69	7	6981	234	29945256
Lower respiratory tract infection	26.63	17.69	32	6956	26682	29918808
Nephrogenic systemic fibrosis	23.71	17.69	14	6974	4357	29941133
Drug ineffective	22.42	17.69	28	6960	340359	29605131
Cerebral malaria	22.09	17.69	3	6985	0	29945490
Malaria	22.08	17.69	6	6982	235	29945255
Increased bronchial secretion	21.44	17.69	9	6979	1350	29944140
Infected skin ulcer	20.93	17.69	9	6979	1431	29944059
Alveolar proteinosis	20.80	17.69	6	6982	293	29945197
Bradycardia	20.03	17.69	46	6942	65480	29880010
Body mass index decreased	19.28	17.69	5	6983	163	29945327
Cutaneous extramedullary haemopoiesis	18.80	17.69	3	6985	6	29945484
Blood magnesium decreased	18.43	17.69	13	6975	5470	29940020

Pharmacologic Action:

Source	Code	Description
ATC	M09AA72	MUSCULO-SKELETAL SYSTEM OTHER DRUGS FOR DISORDERS OF THE MUSCULO-SKELETAL SYSTEM OTHER DRUGS FOR DISORDERS OF THE MUSCULO-SKELETAL SYSTEM Quinine and derivatives
ATC	P01BC01	ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS ANTIPROTOZOALS ANTIMALARIALS Methanolquinolines
FDA EPC	N0000175482	Antimalarial
MeSH PA	D000700	Analgesics
MeSH PA	D018712	Analgesics, Non-Narcotic
MeSH PA	D000890	Anti-Infective Agents
MeSH PA	D000962	Antimalarials
MeSH PA	D000977	Antiparasitic Agents
MeSH PA	D000981	Antiprotozoal Agents
MeSH PA	D002491	Central Nervous System Agents
MeSH PA	D009125	Muscle Relaxants, Central
MeSH PA	D009465	Neuromuscular Agents
MeSH PA	D018373	Peripheral Nervous System Agents
MeSH PA	D018689	Sensory System Agents
CHEBI has role	CHEBI:38068	antimalarials
CHEBI has role	CHEBI:51371	muscle relaxants

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Falciparum malaria	indication	62676009	DOID:14067
Chloroquine Resistant Plasmodium Falciparum Malaria	indication
Babesiosis	off-label use	21061004	DOID:9643
Atrial flutter	contraindication	5370000
Torsades de pointes	contraindication	31722008
End stage renal disease	contraindication	46177005	DOID:784
Atrial fibrillation	contraindication	49436004	DOID:0060224
Neuromuscular block, function	contraindication	55394004
Black water fever	contraindication	56625005	DOID:14068
Acute nephropathy	contraindication	58574008
Optic neuritis	contraindication	66760008	DOID:1210
Thrombotic thrombocytopenic purpura	contraindication	78129009	DOID:10772
Myasthenia gravis	contraindication	91637004	DOID:437
Hemolytic uremic syndrome	contraindication	111407006	DOID:12554
Anemia due to enzyme deficiency	contraindication	111577008
Prolonged QT interval	contraindication	111975006
Disease of liver	contraindication	235856003	DOID:409
Hypoglycemic disorder	contraindication	237630007
Thrombocytopenic disorder	contraindication	302215000	DOID:1588
Congenital long QT syndrome	contraindication	442917000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	12.44	acidic
pKa2	8.02	Basic
pKa3	4.1	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source
Hemoglobin subunit alpha	Secreted	P69905	HBA_HUMAN				WOMBAT-PK
Potassium voltage-gated channel subfamily H member 2	Ion channel	Q12809	KCNH2_HUMAN				WOMBAT-PK
Equilibrative nucleoside transporter 4	Transporter	Q7RTT9	S29A4_HUMAN	INHIBITOR	Ki	4.57	IUPHAR
Potassium voltage-gated channel subfamily B member 2	Ion channel	Q92953	KCNB2_HUMAN	BLOCKER	IC50	4.90	IUPHAR
Multidrug resistance protein 1	Transporter	P08183	MDR1_HUMAN		Ki	4.92	CHEMBL
Solute carrier family 22 member 1	Transporter	O15245	S22A1_HUMAN		IC50	4.29	CHEMBL
Sodium channel alpha subunits; brain (Types I, II, III)	Ion channel	P35498 Q99250 Q9NY46	SCN1A_HUMAN SCN2A_HUMAN SCN3A_HUMAN		IC50	5.36	CHEMBL

External reference:

ID	Source
D08460	KEGG_DRUG
6183-68-2	SECONDARY_CAS_RN
4018620	VANDF
4019926	VANDF
C0034417	UMLSCUI
CHEBI:15854	CHEBI
QI9	PDB_CHEM_ID
DB00468	DRUGBANK_ID
CHEMBL2359966	ChEMBL_ID
CHEMBL170	ChEMBL_ID
D011803	MESH_DESCRIPTOR_UI
3034034	PUBCHEM_CID
2510	IUPHAR_LIGAND_ID
A7V27PHC7A	UNII
647128	RXNORM
5023	MMSL
5405	MMSL
84102	MMSL
d00366	MMSL
002934	NDDF
002935	NDDF
373497008	SNOMEDCT_US
47065008	SNOMEDCT_US
47857006	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Quinine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	0093-3002	CAPSULE	324 mg	ORAL	ANDA	31 sections
Qualaquin	HUMAN PRESCRIPTION DRUG LABEL	1	13310-153	CAPSULE	324 mg	ORAL	NDA	32 sections
QUALAQUIN	HUMAN PRESCRIPTION DRUG LABEL	1	16590-595	CAPSULE	324 mg	ORAL	NDA	32 sections
Qualaquin	HUMAN PRESCRIPTION DRUG LABEL	1	49708-153	CAPSULE	324 mg	ORAL	NDA	32 sections
QUININE SULFATE	HUMAN PRESCRIPTION DRUG LABEL	1	50742-238	CAPSULE	324 mg	ORAL	ANDA	21 sections
Quinine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	53489-700	CAPSULE	324 mg	ORAL	NDA authorized generic	32 sections
Quinine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	65162-811	CAPSULE	324 mg	ORAL	ANDA	20 sections
Quinine Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	68084-947	CAPSULE	324 mg	ORAL	NDA authorized generic	31 sections
QUININE SULFATE	HUMAN PRESCRIPTION DRUG LABEL	1	68180-560	CAPSULE	324 mg	ORAL	ANDA	20 sections