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Identification
NamePrimaquine
Accession NumberDB01087  (APRD00604)
TypeSmall Molecule
GroupsApproved
Description

An aminoquinoline that is given by mouth to produce a radical cure and prevent relapse of vivax and ovale malarias following treatment with a blood schizontocide. It has also been used to prevent transmission of falciparum malaria by those returning to areas where there is a potential for re-introduction of malaria. Adverse effects include anemias and GI disturbances. (From Martindale, The Extra Pharmacopeia, 30th ed, p404)

Structure
Thumb
Synonyms
6-Methoxy-8-(4-amino-1-methylbutylamino)quinoline
8-((4-Amino-1-methylbutyl)amino)-6-methoxyquinoline
8-(4-Amino-1-methylbutylamino)-6-methoxyquinoline
Neo-quipenyl
Primachin
Primachinum
Primaquin
Primaquina
Primaquinum
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Primaquinetablet26.3 mgoralSanofi Aventis Canada Inc1945-12-31Not applicableCanada
Primaquine Phosphatetablet, film coated15 mg/1oralSanofi Aventis U.S. Llc2011-04-15Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Primaquine Phosphatetablet26.3 mg/1oralPd Rx Pharmaceuticals, Inc.2010-01-01Not applicableUs
Primaquine Phosphatetablet15 mg/1oralBayshore Pharmaceuticals, LLC2014-08-01Not applicableUs
Primaquine Phosphatetablet, film coated15 mg/1oralGolden State Medical Supply, Inc.2014-05-08Not applicableUs
Primaquine Phosphatetablet, film coated26.3 mg/1oralAlvogen, Inc.2011-12-08Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
Neo-QuipenylNot Available
PrimachinNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Primaquine phosphate
ThumbNot applicableDBSALT001188
Categories
UNIIMVR3634GX1
CAS number90-34-6
WeightAverage: 259.3467
Monoisotopic: 259.168462309
Chemical FormulaC15H21N3O
InChI KeyInChIKey=INDBQLZJXZLFIT-UHFFFAOYSA-N
InChI
InChI=1S/C15H21N3O/c1-11(5-3-7-16)18-14-10-13(19-2)9-12-6-4-8-17-15(12)14/h4,6,8-11,18H,3,5,7,16H2,1-2H3
IUPAC Name
N4-(6-methoxyquinolin-8-yl)pentane-1,4-diamine
SMILES
COC1=CC(NC(C)CCCN)=C2N=CC=CC2=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as hydroxyquinolines. These are compounds containing a quinoline moiety bearing a hydroxyl group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassQuinolines and derivatives
Sub ClassHydroxyquinolines
Direct ParentHydroxyquinolines
Alternative Parents
Substituents
  • Hydroxyquinoline
  • Methoxyaniline
  • Anisole
  • Secondary aliphatic/aromatic amine
  • Alkyl aryl ether
  • Benzenoid
  • Pyridine
  • Heteroaromatic compound
  • Azacycle
  • Secondary amine
  • Ether
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of malaria.
PharmacodynamicsPrimaquine is an antimalarial agent and is the essential co-drug with chloroquine in treating all cases of malaria. In the blood, malaria parasites break down a part of the red blood cells known as haemoglobin. When this happens haemoglobin is divided into two parts; haem and globin. Haem is toxic to the malaria parasite. To prevent it from being damaged, the malaria parasite produces an chemical which converts the toxic haem into a non-toxic product. Primaquine acts by interfering with a part of the parasite (mitochondria) that is responsible for supplying it with energy. Without energy the parasite dies. This stops the infection from continuing and allows the person to recover. Primaquine kills the intrahepatic form of Plasmodium vivax and Plasmodium ovale, and thereby prevents the development of the erythrocytic forms that are responsible for relapses (it also kills gametocytes). Primaquine is not used in the prevention of malaria, only in the treatment. It has insignificant activity against the asexual blood forms of the parasite and therefore it is always used in conjunction with a blood schizonticide and never as a single agent. Primaquine has gametocytocidal activity against all plasmodia, including P. falciparum.
Mechanism of actionPrimaquine's mechanism of action is not well understood. It may be acting by generating reactive oxygen species or by interfering with the electron transport in the parasite. Also, although its mechanism of action is unclear, primaquine may bind to and alter the properties of protozoal DNA.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half life3.7-7.4 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Plasmodium
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9776
Blood Brain Barrier+0.9787
Caco-2 permeable-0.5622
P-glycoprotein substrateSubstrate0.8018
P-glycoprotein inhibitor INon-inhibitor0.8782
P-glycoprotein inhibitor IINon-inhibitor0.7681
Renal organic cation transporterInhibitor0.5501
CYP450 2C9 substrateNon-substrate0.8703
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.5723
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.93
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorNon-inhibitor0.831
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5057
Ames testAMES toxic0.9106
CarcinogenicityNon-carcinogens0.9283
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4474 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7858
hERG inhibition (predictor II)Inhibitor0.8162
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Tabletoral26.3 mg
Tabletoral15 mg/1
Tabletoral26.3 mg/1
Tablet, film coatedoral15 mg/1
Tablet, film coatedoral26.3 mg/1
Prices
Unit descriptionCostUnit
Primaquin phosphate powder18.2USD g
Primaquine 26.3 mg tablet1.51USD tablet
Primaquine Phosphate 15 mg Tablet0.43USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point< 25 °CPhysProp
boiling point177 °C at 2.00E-01 mm HgPhysProp
logP2.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0564 mg/mLALOGPS
logP2.76ALOGPS
logP1.64ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)17.11ChemAxon
pKa (Strongest Basic)10.2ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area60.17 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity78.51 m3·mol-1ChemAxon
Polarizability29.92 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General References
  1. Mihaly GW, Ward SA, Edwards G, Nicholl DD, Orme ML, Breckenridge AM: Pharmacokinetics of primaquine in man. I. Studies of the absolute bioavailability and effects of dose size. Br J Clin Pharmacol. 1985 Jun;19(6):745-50. [PubMed:4027117 ]
  2. ALVING AS, ARNOLD J, HOCKWALD RS, CLAYMAN CB, DERN RJ, BEUTLER E, FLANAGAN CL: Potentiation of the curative action of primaquine in vivax malaria by quinine and chloroquine. J Lab Clin Med. 1955 Aug;46(2):301-6. [PubMed:13242948 ]
  3. Hill DR, Baird JK, Parise ME, Lewis LS, Ryan ET, Magill AJ: Primaquine: report from CDC expert meeting on malaria chemoprophylaxis I. Am J Trop Med Hyg. 2006 Sep;75(3):402-15. [PubMed:16968913 ]
  4. Cohen RJ, Sachs JR, Wicker DJ, Conrad ME: Methemoglobinemia provoked by malarial chemoprophylaxis in Vietnam. N Engl J Med. 1968 Nov 21;279(21):1127-31. [PubMed:5686480 ]
  5. Coleman MD, Coleman NA: Drug-induced methaemoglobinaemia. Treatment issues. Drug Saf. 1996 Jun;14(6):394-405. [PubMed:8828017 ]
External Links
ATC CodesP01BA03
AHFS Codes
  • 08:30.08
PDB Entries
FDA labelDownload (105 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AbirateroneThe serum concentration of Primaquine can be increased when it is combined with Abiraterone.
AcepromazineThe serum concentration of Acepromazine can be increased when it is combined with Primaquine.
AgomelatineThe serum concentration of Agomelatine can be increased when it is combined with Primaquine.
AripiprazoleThe serum concentration of Aripiprazole can be increased when it is combined with Primaquine.
ArtemetherThe risk or severity of adverse effects can be increased when Artemether is combined with Primaquine.
BendamustineThe serum concentration of Bendamustine can be increased when it is combined with Primaquine.
BexaroteneThe serum concentration of Primaquine can be decreased when it is combined with Bexarotene.
BortezomibThe metabolism of Bortezomib can be decreased when combined with Primaquine.
BosentanThe serum concentration of Primaquine can be decreased when it is combined with Bosentan.
CitalopramPrimaquine may increase the QTc-prolonging activities of Citalopram.
ClozapineThe serum concentration of Clozapine can be increased when it is combined with Primaquine.
CobicistatThe serum concentration of Primaquine can be increased when it is combined with Cobicistat.
DabrafenibThe serum concentration of Primaquine can be decreased when it is combined with Dabrafenib.
DapsoneThe risk or severity of adverse effects can be increased when Primaquine is combined with Dapsone.
DarunavirThe serum concentration of Primaquine can be increased when it is combined with Darunavir.
DeferasiroxThe serum concentration of Primaquine can be decreased when it is combined with Deferasirox.
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Primaquine.
DofetilidePrimaquine may increase the QTc-prolonging activities of Dofetilide.
DuloxetineThe serum concentration of Duloxetine can be increased when it is combined with Primaquine.
FluoxetineThe metabolism of Primaquine can be decreased when combined with Fluoxetine.
FluvoxamineThe metabolism of Fluvoxamine can be decreased when combined with Primaquine.
GoserelinGoserelin may increase the QTc-prolonging activities of Primaquine.
IvabradineIvabradine may increase the QTc-prolonging activities of Primaquine.
LeuprolideLeuprolide may increase the QTc-prolonging activities of Primaquine.
LumefantrineThe risk or severity of adverse effects can be increased when Primaquine is combined with Lumefantrine.
MefloquineThe risk or severity of adverse effects can be increased when Primaquine is combined with Mefloquine.
MifepristoneMifepristone may increase the QTc-prolonging activities of Primaquine.
MitotaneThe serum concentration of Primaquine can be decreased when it is combined with Mitotane.
Nitric OxideThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Primaquine.
OctreotideOctreotide may increase the QTc-prolonging activities of Primaquine.
OxibendazoleThe serum concentration of Oxibendazole can be decreased when it is combined with Primaquine.
PanobinostatThe serum concentration of Primaquine can be increased when it is combined with Panobinostat.
Peginterferon alfa-2bThe serum concentration of Primaquine can be decreased when it is combined with Peginterferon alfa-2b.
PentoxifyllineThe serum concentration of Pentoxifylline can be increased when it is combined with Primaquine.
PhenytoinThe metabolism of Primaquine can be increased when combined with Phenytoin.
PirfenidoneThe serum concentration of Pirfenidone can be increased when it is combined with Primaquine.
PomalidomideThe serum concentration of Pomalidomide can be increased when it is combined with Primaquine.
PrilocaineThe risk or severity of adverse effects can be increased when Primaquine is combined with Prilocaine.
QuinacrineThe serum concentration of Quinacrine can be decreased when it is combined with Primaquine.
RasagilineThe serum concentration of Rasagiline can be increased when it is combined with Primaquine.
RitonavirThe metabolism of Primaquine can be decreased when combined with Ritonavir.
SiltuximabThe serum concentration of Primaquine can be decreased when it is combined with Siltuximab.
Sodium NitriteThe risk or severity of adverse effects can be increased when Primaquine is combined with Sodium Nitrite.
St. John's WortThe serum concentration of Primaquine can be decreased when it is combined with St. John&#39;s Wort.
TasimelteonThe serum concentration of Tasimelteon can be increased when it is combined with Primaquine.
ThiabendazoleThe serum concentration of Thiabendazole can be decreased when it is combined with Primaquine.
TiclopidineThe metabolism of Primaquine can be decreased when combined with Ticlopidine.
TizanidineThe serum concentration of Tizanidine can be increased when it is combined with Primaquine.
TocilizumabThe serum concentration of Primaquine can be decreased when it is combined with Tocilizumab.
Food Interactions
  • Take with food to decrease dyspepsia.

Targets

1. Fe(II)-protoporphyrin IX
Kind
Small molecule
Organism
Plasmodium falciparum
Pharmacological action
yes
Actions
antagonist
References
  1. Dorn A, Vippagunta SR, Matile H, Jaquet C, Vennerstrom JL, Ridley RG: An assessment of drug-haematin binding as a mechanism for inhibition of haematin polymerisation by quinoline antimalarials. Biochem Pharmacol. 1998 Mar 15;55(6):727-36. [PubMed:9586944 ]
  2. Fitch CD: Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs. Life Sci. 2004 Mar 5;74(16):1957-72. [PubMed:14967191 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
other/unknown
General Function:
Structural molecule activity
Specific Function:
Blocks interferon-dependent interphase and stimulates DNA synthesis in cells. Involved in the translational regulation of the human papillomavirus type 16 E7 mRNA (HPV16 E7).
Gene Name:
KRT7
Uniprot ID:
P08729
Molecular Weight:
51385.11 Da
References
  1. Heard CM, Monk BV, Modley AJ: Binding of primaquine to epidermal membranes and keratin. Int J Pharm. 2003 May 12;257(1-2):237-44. [PubMed:12711178 ]
  2. Basso LG, Rodrigues RZ, Naal RM, Costa-Filho AJ: Effects of the antimalarial drug primaquine on the dynamic structure of lipid model membranes. Biochim Biophys Acta. 2011 Jan;1808(1):55-64. doi: 10.1016/j.bbamem.2010.08.009. Epub 2010 Aug 14. [PubMed:20713019 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Nadph dehydrogenase (quinone) activity
Specific Function:
The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinones involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.
Gene Name:
NQO2
Uniprot ID:
P16083
Molecular Weight:
25918.4 Da
References
  1. Graves PR, Kwiek JJ, Fadden P, Ray R, Hardeman K, Coley AM, Foley M, Haystead TA: Discovery of novel targets of quinoline drugs in the human purine binding proteome. Mol Pharmacol. 2002 Dec;62(6):1364-72. [PubMed:12435804 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitorinducer
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
General Function:
Vitamin d 24-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP1A1
Uniprot ID:
P04798
Molecular Weight:
58164.815 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
General Function:
Oxygen binding
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, retinoid and xenobiotics. Preferentially oxidizes 17beta-estradiol to the carcinogenic 4-hydroxy derivative, and a variety of procarcinogenic compou...
Gene Name:
CYP1B1
Uniprot ID:
Q16678
Molecular Weight:
60845.33 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on September 22, 2015 11:04