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targets (3) enzymes (5)
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Identification
Name Primaquine
Accession Number DB01087 (APRD00604)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Neo-Quipenyl
Primachin
Brand mixtures Not Available
Categories
  • Antimalarials
  • Antiprotozoal Agents
  • Antimalarial Agents
CAS number 90-34-6
Weight Average: 259.3467
Monoisotopic: 259.168462309
Chemical Formula C15H21N3O
InChI Key InChIKey=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
Plain Text
IUPAC Name
N-(5-aminopentan-2-yl)-6-methoxyquinolin-8-amine
SMILES
COC1=CC(NC(C)CCCN)=C2N=CC=CC2=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Hydroxyquinolines
Substructures
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Pyridines and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Hydroxyquinolines
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • (Iso)quinolines and Derivatives
  • Phenyl Esters
  • Anilines
Pharmacology
Indication For the treatment of malaria.
Pharmacodynamics Primaquine 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 action Primaquine'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.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism
Not Available
Route of elimination Not Available
Half life 3.7-7.4 hours
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Plasmodium
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Primaquin phosphate powder 18.2 USD g
Primaquine 26.3 mg tablet 1.51 USD tablet
Primaquine Phosphate 15 mg Tablet 0.43 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point < 25 °C PhysProp
boiling point 177 °C at 2.00E-01 mm Hg PhysProp
logP 2.1 Not Available
Predicted Properties
Property Value Source
water solubility 5.64e-02 g/l ALOGPS
logP 2.76 ALOGPS
logP 1.64 ChemAxon
logS -3.7 ALOGPS
pKa (strongest acidic) 17.11 ChemAxon
pKa (strongest basic) 10.2 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 60.17 ChemAxon
rotatable bond count 6 ChemAxon
refractivity 78.51 ChemAxon
polarizability 29.92 ChemAxon
References
Synthesis Reference Not 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
Resource Link
KEGG Compound C07627 Link_out
PubChem Compound 4908 Link_out
PubChem Substance 46508222 Link_out
ChemSpider 4739 Link_out
BindingDB 50203193 Link_out
ChEBI 8405 Link_out
ChEMBL 8405 Link_out
Therapeutic Targets Database DAP000216 Link_out
PharmGKB PA451103 Link_out
Drug Product Database 2017776 Link_out
Drugs.com http://www.drugs.com/cdi/primaquine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Primaquine Link_out
ATC Codes
  • P01BA03
AHFS Codes
  • 08:30.08
PDB Entries
FDA label show (105 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Artemether Primaquine may increase the adverse effects of artemether. Combination therapy is contraindicated unless there are no other treatment options.
Lumefantrine Primaquine may increase the adverse effects of lumefantrine. Combination therapy is contraindicated unless there are no other treatment options.
Tacrine The 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.
Thiothixene The 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.
Tizanidine Primaquine 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. Ferriprotoporphyrin IX

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
  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

Pharmacological action: unknown
Actions: other/unknown
Organism class: human
UniProt ID: P08729 Link_out
Gene: KRT7
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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]

Pharmacological action: unknown
Actions: inhibitor

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

Organism class: human
UniProt ID: P16083 Link_out
Gene: NQO2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate, inhibitor

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 xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate, inhibitor, inducer

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 N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

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

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inducer

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

UniProt ID: P04798 Link_out
Gene: CYP1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inducer

Participates in the metabolism of an as-yet-unknown biologically active molecule that is a participant in eye development

UniProt ID: Q16678 Link_out
Gene: CYP1B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19