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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
SynonymLanguageCode
6-Methoxy-8-(4-amino-1-methylbutylamino)quinolineNot AvailableNot Available
8-((4-Amino-1-methylbutyl)amino)-6-methoxyquinolineNot AvailableNot Available
8-(4-Amino-1-methylbutylamino)-6-methoxyquinolineNot AvailableNot Available
Neo-quipenylNot AvailableNot Available
PrimachinNot AvailableNot Available
PrimachinumNot AvailableNot Available
PrimaquinNot AvailableNot Available
PrimaquinaNot AvailableNot Available
PrimaquinumNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
Neo-QuipenylNot Available
PrimachinNot Available
Brand mixturesNot Available
Categories
CAS number90-34-6
WeightAverage: 259.3467
Monoisotopic: 259.168462309
Chemical FormulaC15H21N3O
InChI KeyINDBQLZJXZLFIT-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
N-(5-aminopentan-2-yl)-6-methoxyquinolin-8-amine
SMILES
COC1=CC(NC(C)CCCN)=C2N=CC=CC2=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassQuinolines and Derivatives
SubclassAminoquinolines and Derivatives
Direct parentAminoquinolines and Derivatives
Alternative parentsHydroxyquinolines; Anisoles; Alkyl Aryl Ethers; Pyridines and Derivatives; Secondary Amines; Polyamines; Monoalkylamines
Substituentsphenol ether; anisole; alkyl aryl ether; pyridine; benzene; secondary amine; ether; polyamine; primary amine; amine; primary aliphatic amine; organonitrogen compound
Classification descriptionThis compound belongs to the aminoquinolines and derivatives. These are organic compounds containing an amino group attached to a quinoline ring system.
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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
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
Property Value Probability
Human Intestinal Absorption + 0.9776
Blood Brain Barrier + 0.9787
Caco-2 permeable - 0.5622
P-glycoprotein substrate Substrate 0.8018
P-glycoprotein inhibitor I Non-inhibitor 0.8782
P-glycoprotein inhibitor II Non-inhibitor 0.7681
Renal organic cation transporter Inhibitor 0.5501
CYP450 2C9 substrate Non-substrate 0.8703
CYP450 2D6 substrate Substrate 0.8918
CYP450 3A4 substrate Substrate 0.5723
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 substrate Non-inhibitor 0.93
CYP450 2D6 substrate Inhibitor 0.8932
CYP450 2C19 substrate Inhibitor 0.8994
CYP450 3A4 substrate Non-inhibitor 0.831
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5057
Ames test AMES toxic 0.9106
Carcinogenicity Non-carcinogens 0.9283
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.4474 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7858
hERG inhibition (predictor II) Inhibitor 0.8162
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
Packagers
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Primaquin phosphate powder18.2USDg
Primaquine 26.3 mg tablet1.51USDtablet
Primaquine Phosphate 15 mg Tablet0.43USDtablet
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 solubility5.64e-02 g/lALOGPS
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 area60.17ChemAxon
rotatable bond count6ChemAxon
refractivity78.51ChemAxon
polarizability29.92ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  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
  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
  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
  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
  5. Coleman MD, Coleman NA: Drug-induced methaemoglobinaemia. Treatment issues. Drug Saf. 1996 Jun;14(6):394-405. Pubmed
External Links
ResourceLink
KEGG CompoundC07627
PubChem Compound4908
PubChem Substance46508222
ChemSpider4739
BindingDB50203193
ChEBI8405
ChEMBLCHEMBL506
Therapeutic Targets DatabaseDAP000216
PharmGKBPA451103
Drug Product Database2017776
Drugs.comhttp://www.drugs.com/cdi/primaquine.html
WikipediaPrimaquine
ATC CodesP01BA03
AHFS Codes
  • 08:30.08
PDB Entries
FDA labelshow(105 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
ArtemetherPrimaquine may increase the adverse effects of artemether. Combination therapy is contraindicated unless there are no other treatment options.
LumefantrinePrimaquine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.
TacrineThe metabolism of Tacrine, a CYP1A2 substrate, may be reduced by strong CYP1A2 inhibitors such as Primaquine. Consider modifying therapy to avoid Tacrine toxicity. Monitor the efficacy and toxicity of Tacrine if Primaquine is initiated, discontinued or if the dose is changed.
ThiothixeneThe strong CYP1A2 inhibitor, Primaquine, may decrease the metabolism and clearance of Thiothixene, a CYP1A2 substrate. Consider alternate therapy or monitor for changes in Thiothixene therapeutic and adverse effects if Primaquine is initiated, discontinued or dose changed.
TizanidinePrimaquine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
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

Components

Name UniProt ID Details

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
  2. Fitch CD: Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs. Life Sci. 2004 Mar 5;74(16):1957-72. Pubmed

2. Keratin, type II cytoskeletal 7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: other/unknown

Components

Name UniProt ID Details
Keratin, type II cytoskeletal 7 P08729 Details

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
  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. 2010 Aug 14. Pubmed

3. Ribosyldihydronicotinamide dehydrogenase [quinone]

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Ribosyldihydronicotinamide dehydrogenase [quinone] P16083 Details

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

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor inducer

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

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. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

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. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 1A1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 1A1 P04798 Details

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. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 1B1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 1B1 Q16678 Details

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. Epub 2009 Nov 24. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13