PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
pyrimethamine

2D structure

Overview

Generic Names: CD; Chloridin; Chloridine; Chloridyn; Diaminopyritamin; Ethylpyrimidine; Pirimetamin; Pirimetamina; Primethamine; Pyremethamine; Pyrimethamin; Pyrimethamine Hcl
Trade Names: Darachlor; Daraclor; Darapram; Daraprim; Daraprime; Disulone; Erbaprelina; Fansidar; Khloridin; Malacid; Malocid; Malocide; Maloprim; Pirimecidan; Tindurin; Tinduring
Brand Mixtures: Fansidar Tablets (Pyrimethamine + Sulfadoxine); Quinnoxine-S (Pyrimethamine + Sulfaquinoxaline); Sulfaquinoxaline-S Liq (Pyrimethamine + Sulfaquinoxaline)
PharmGKB Accession Id: PA451193

Description

One of the folic acid antagonists that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis. PubChem (source: Drug Bank)

Indication

For the treatment of toxoplasmosis and acute malaria; For the prevention of malaria in areas non-resistant to pyrimethamine (source: Drug Bank)

ATC Therapeutic Category

  • P01BD:Diaminopyrimidines

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Pyrimethamine inhibits the dihydrofolate reductase of plasmodia and thereby blocks the biosynthesis of purines and pyrimidines, which are essential for DNA synthesis and cell multiplication. This leads to failure of nuclear division at the time of schizont formation in erythrocytes and liver. (source: Drug Bank)

Pharmacology

Pyrimethamine is an antiparasitic compound commonly used as an adjunct in the treatment of uncomplicated, chloroquine resistant, P. falciparum malaria. Pyrimethamine is a folic acid antagonist and the rationale for its therapeutic action is based on the differential requirement between host and parasite for nucleic acid precursors involved in growth. This activity is highly selective against plasmodia and Toxoplasma gondii. Pyrimethamine possesses blood schizonticidal and some tissue schizonticidal activity against malaria parasites of humans. However, the 4-amino-quinoline compounds are more effective against the erythrocytic schizonts. It does not destroy gametocytes, but arrests sporogony in the mosquito. The action of pyrimethamine against Toxoplasma gondii is greatly enhanced when used in conjunction with sulfonamides. (source: Drug Bank)

Food Interactions

Folic acid needs increased.
Take with food to reduce irritation. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic (source: Drug Bank)

Protein Binding

87% (source: Drug Bank)

Absorption

Well absorbed with peak levels occurring between 2 to 6 hours following administration (source: Drug Bank)

Isomeric SMILES Code:

CCc1c(c(nc(n1)N)N)c2ccc(cc2)Cl (source: Drug Bank)

In-Depth Annotations (In-Depth Annotation)

  1. rs1695 at chr11:67109265 in GSTP1
    The non-synonymous SNP has been associated with reduced enzyme activity and anticancer drug resistance and toxicity.
    Variant Name:
    GSTP1: I105V; GSTP1*B
    Related Drugs:
    cisplatin, cyclophosphamide, doxorubicin, etoposide, oxaliplatin, pyrimethamine
    Evidence:
    http://www.pharmgkb.org/.../variant.jsp
  2. rs1138272 at chr11:67110155 in GSTP1
    This variant is less well studied and its pharmacogenetic significance is unclear. The variant allele is almost always found in linkage disequilibrium with GSTP1 I105V SNP.
    Variant Name:
    GSTP1: A114V
    Related Drugs:
    cisplatin, cyclophosphamide, doxorubicin, etoposide, oxaliplatin, pyrimethamine
    Evidence:
    http://www.pharmgkb.org/.../variant.jsp
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Has annotations
GSTP1
  •   
  •   
  •   
  •   
  •   
Variants

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
DHFR Uncurated Annotation (source: Drug Bank)

A list of non-curated publications that mention this drug along with other drugs is available.

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Epidermal Necrolysis, Toxic
  •   
  • PD
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Hepatitis, Toxic
  •   
  • PD
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Malaria, Falciparum
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Stevens-Johnson Syndrome
  •   
  • PD
  •   
  •   
  •   
Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

  1. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00205
KEGG Compound ID:
C07391
KEGG Drug ID:
D00488
PubChem Compound ID:
4993
PubChem Substance ID:
9595

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Non-Curated Publications

A list of non-curated publications that mention this drug is available.

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
Add New Alternate Name
Add New ATC Term
Add Cross Reference
Add a metabolite
Add a text annotation
Add a drug target
hint: enter a gene
    Add a drug interaction
    hint: enter a drug
    PharmGKB® is a registered trademark of HHS and is financially supported by NIH/NIGMS. It is managed at Stanford University (GM61374).
    ©2001-2010 PharmGKB.