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Identification
NamePyrimethamine
Accession NumberDB00205  (APRD00599)
TypeSmall Molecule
GroupsApproved, Vet Approved
DescriptionOne of the folic acid antagonists that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis. [PubChem]
Structure
Thumb
Synonyms
2,4-Diamino-5-(4-chlorophenyl)-6-ethylpyrimidine
2,4-Diamino-5-(P-chlorophenyl)-6-ethylpyrimidine
2,4-Diamino-5-chlorophenyl-6-ethylpyrimidine
5-(4-Chlorophenyl)-6-ethyl-2,4-diaminopyrimidine
5-(4-Chlorophenyl)-6-ethyl-2,4-pyrimidinediamine
5-(4'-Chlorophenyl)-2,4-diamino-6-ethylpyrimidine
CD
Chloridine
Chloridyn
Diaminopyritamin
Ethylpyrimidine
Pirimetamina
Primethamine
Pyrimethaminum
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Daraprimtablet25 mg/1oralKAISER FOUNDATION HOSPITALS2011-04-20Not applicableUs
Daraprimtablet25 mgoralAmedra Pharmaceuticals LLC1952-12-312013-06-01Canada
Daraprimtablet25 mg/1oralAmedra Pharmaceuticals LLC1953-01-23Not applicableUs
Daraprimtablet25 mg/1oralREMEDYREPACK INC.2013-02-26Not applicableUs
Daraprimtablet25 mg/1oralTuring Pharmaceuticals Llc1953-01-23Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixtures
NameLabellerIngredients
Fansidar TabletsHoffmann La Roche Limited
Pyrimethamine LeucovorinSouth Coast Specialty Compounding, Inc. D/B/A Park Compounding
Salts
Name/CASStructureProperties
Pyrimethamine Hydrochloride
19085-09-7
Thumb
  • InChI Key: JZCLIFPQURTYFA-UHFFFAOYSA-N
  • Monoisotopic Mass: 284.059551882
  • Average Mass: 285.172
DBSALT000385
Categories
UNIIZ3614QOX8W
CAS number58-14-0
WeightAverage: 248.711
Monoisotopic: 248.082874143
Chemical FormulaC12H13ClN4
InChI KeyInChIKey=WKSAUQYGYAYLPV-UHFFFAOYSA-N
InChI
InChI=1S/C12H13ClN4/c1-2-9-10(11(14)17-12(15)16-9)7-3-5-8(13)6-4-7/h3-6H,2H2,1H3,(H4,14,15,16,17)
IUPAC Name
5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine
SMILES
CCC1=C(C(N)=NC(N)=N1)C1=CC=C(Cl)C=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylpyrimidines. These are polycyclic aromatic compounds containing a benzene ring linked to a pyrimidine ring through a CC or CN bond. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazines
Sub ClassPyrimidines and pyrimidine derivatives
Direct ParentPhenylpyrimidines
Alternative Parents
Substituents
  • 5-phenylpyrimidine
  • Halobenzene
  • Chlorobenzene
  • Aminopyrimidine
  • Imidolactam
  • Benzenoid
  • Primary aromatic amine
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl chloride
  • Heteroaromatic compound
  • Azacycle
  • Hydrocarbon derivative
  • Primary amine
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of toxoplasmosis and acute malaria; For the prevention of malaria in areas non-resistant to pyrimethamine
PharmacodynamicsPyrimethamine 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.
Mechanism of actionPyrimethamine 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.
Related Articles
AbsorptionWell absorbed with peak levels occurring between 2 to 6 hours following administration
Volume of distributionNot Available
Protein binding87%
Metabolism

Hepatic

Route of eliminationNot Available
Half life96 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+0.9973
Blood Brain Barrier+0.9383
Caco-2 permeable+0.6217
P-glycoprotein substrateNon-substrate0.5822
P-glycoprotein inhibitor INon-inhibitor0.8643
P-glycoprotein inhibitor IINon-inhibitor0.9045
Renal organic cation transporterNon-inhibitor0.7451
CYP450 2C9 substrateNon-substrate0.8103
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6582
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.7586
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6667
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.8016
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7833 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9337
hERG inhibition (predictor II)Non-inhibitor0.8586
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Glaxosmithkline llc
Packagers
Dosage forms
FormRouteStrength
Tabletoral25 mg/1
Tabletoral25 mg
Tabletoral
Capsuleoral
Prices
Unit descriptionCostUnit
Pyrimethamine powder8.88USD g
Daraprim 25 mg tablet0.98USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point233.5 °CPhysProp
water solubility121 mg/LNot Available
logP2.69HANSCH,C ET AL. (1995)
pKa7.34 (at 20 °C)PERRIN,DD (1972)
Predicted Properties
PropertyValueSource
Water Solubility0.179 mg/mLALOGPS
logP2.62ALOGPS
logP2.75ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)17.22ChemAxon
pKa (Strongest Basic)7.77ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area77.82 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity71.54 m3·mol-1ChemAxon
Polarizability25.79 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
MSMass Spectrum (Electron Ionization)splash10-0002-2590000000-6434b6f0181741b3ca41View in MoNA
References
Synthesis Reference

DrugSyn.org

US2576939
General References
  1. Gatton ML, Martin LB, Cheng Q: Evolution of resistance to sulfadoxine-pyrimethamine in Plasmodium falciparum. Antimicrob Agents Chemother. 2004 Jun;48(6):2116-23. [PubMed:15155209 ]
  2. Sirichaiwat C, Intaraudom C, Kamchonwongpaisan S, Vanichtanankul J, Thebtaranonth Y, Yuthavong Y: Target guided synthesis of 5-benzyl-2,4-diamonopyrimidines: their antimalarial activities and binding affinities to wild type and mutant dihydrofolate reductases from Plasmodium falciparum. J Med Chem. 2004 Jan 15;47(2):345-54. [PubMed:14711307 ]
External Links
ATC CodesP01BD51P01BD01P01BF04
AHFS Codes
  • 08:30.08
PDB Entries
FDA labelDownload (29.7 KB)
MSDSDownload (74 KB)
Interactions
Drug Interactions
Drug
AceclofenacThe metabolism of Aceclofenac can be decreased when combined with Pyrimethamine.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Pyrimethamine.
AcepromazineThe serum concentration of Acepromazine can be increased when it is combined with Pyrimethamine.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Pyrimethamine.
Acetylsalicylic acidThe metabolism of Acetylsalicylic acid can be decreased when combined with Pyrimethamine.
AlimemazineThe serum concentration of Alimemazine can be increased when it is combined with Pyrimethamine.
AlosetronThe metabolism of Alosetron can be decreased when combined with Pyrimethamine.
AlprazolamThe metabolism of Alprazolam can be decreased when combined with Pyrimethamine.
AminophenazoneThe metabolism of Aminophenazone can be decreased when combined with Pyrimethamine.
AmiodaroneThe metabolism of Amiodarone can be decreased when combined with Pyrimethamine.
AmitriptylineThe metabolism of Amitriptyline can be decreased when combined with Pyrimethamine.
AmodiaquineThe serum concentration of Amodiaquine can be increased when it is combined with Pyrimethamine.
AmprenavirThe metabolism of Amprenavir can be decreased when combined with Pyrimethamine.
AntipyrineThe metabolism of Antipyrine can be decreased when combined with Pyrimethamine.
ApixabanThe metabolism of Apixaban can be decreased when combined with Pyrimethamine.
Arachidonic AcidThe metabolism of Arachidonic Acid can be decreased when combined with Pyrimethamine.
ArformoterolThe metabolism of Arformoterol can be decreased when combined with Pyrimethamine.
ArtemetherThe risk or severity of adverse effects can be increased when Artemether is combined with Pyrimethamine.
ArtemetherThe metabolism of Artemether can be decreased when combined with Pyrimethamine.
AtazanavirThe metabolism of Atazanavir can be decreased when combined with Pyrimethamine.
AzelastineThe metabolism of Azelastine can be decreased when combined with Pyrimethamine.
BexaroteneThe metabolism of Bexarotene can be decreased when combined with Pyrimethamine.
BortezomibThe metabolism of Bortezomib can be decreased when combined with Pyrimethamine.
BosentanThe serum concentration of Bosentan can be increased when it is combined with Pyrimethamine.
BrompheniramineThe metabolism of Brompheniramine can be decreased when combined with Pyrimethamine.
BuprenorphineThe metabolism of Buprenorphine can be decreased when combined with Pyrimethamine.
BupropionThe metabolism of Bupropion can be decreased when combined with Pyrimethamine.
CabozantinibThe metabolism of Cabozantinib can be decreased when combined with Pyrimethamine.
CaffeineThe metabolism of Caffeine can be decreased when combined with Pyrimethamine.
CandesartanThe metabolism of Candesartan can be decreased when combined with Pyrimethamine.
CarbinoxamineThe metabolism of Carbinoxamine can be decreased when combined with Pyrimethamine.
CarvedilolThe serum concentration of Carvedilol can be increased when it is combined with Pyrimethamine.
CelecoxibThe metabolism of Celecoxib can be decreased when combined with Pyrimethamine.
ChlorpromazineThe serum concentration of Chlorpromazine can be increased when it is combined with Pyrimethamine.
ChlorpropamideThe metabolism of Chlorpropamide can be decreased when combined with Pyrimethamine.
CinnarizineThe metabolism of Cinnarizine can be decreased when combined with Pyrimethamine.
CisaprideThe metabolism of Cisapride can be decreased when combined with Pyrimethamine.
ClopidogrelThe metabolism of Clopidogrel can be decreased when combined with Pyrimethamine.
ClozapineThe metabolism of Clozapine can be decreased when combined with Pyrimethamine.
CyclophosphamideThe metabolism of Cyclophosphamide can be decreased when combined with Pyrimethamine.
DapagliflozinThe metabolism of Dapagliflozin can be decreased when combined with Pyrimethamine.
DapsoneThe metabolism of Dapsone can be decreased when combined with Pyrimethamine.
DextromethorphanThe metabolism of Dextromethorphan can be decreased when combined with Pyrimethamine.
DiazepamThe metabolism of Diazepam can be decreased when combined with Pyrimethamine.
DiclofenacThe metabolism of Diclofenac can be decreased when combined with Pyrimethamine.
DicoumarolThe metabolism of Dicoumarol can be decreased when combined with Pyrimethamine.
DiltiazemThe metabolism of Diltiazem can be decreased when combined with Pyrimethamine.
DiphenhydramineThe metabolism of Diphenhydramine can be decreased when combined with Pyrimethamine.
DolasetronThe metabolism of Dolasetron can be decreased when combined with Pyrimethamine.
DonepezilThe metabolism of Donepezil can be decreased when combined with Pyrimethamine.
DopamineThe metabolism of Dopamine can be decreased when combined with Pyrimethamine.
DorzolamideThe metabolism of Dorzolamide can be decreased when combined with Pyrimethamine.
DoxepinThe metabolism of Doxepin can be decreased when combined with Pyrimethamine.
DronabinolThe serum concentration of Dronabinol can be increased when it is combined with Pyrimethamine.
EletriptanThe metabolism of Eletriptan can be decreased when combined with Pyrimethamine.
EpoprostenolThe metabolism of Epoprostenol can be decreased when combined with Pyrimethamine.
EstradiolThe metabolism of Estradiol can be decreased when combined with Pyrimethamine.
EstroneThe metabolism of Estrone can be decreased when combined with Pyrimethamine.
EszopicloneThe metabolism of Eszopiclone can be decreased when combined with Pyrimethamine.
EtodolacThe metabolism of Etodolac can be decreased when combined with Pyrimethamine.
EtoricoxibThe metabolism of Etoricoxib can be decreased when combined with Pyrimethamine.
EtravirineThe metabolism of Etravirine can be decreased when combined with Pyrimethamine.
FesoterodineThe serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Pyrimethamine.
FlunarizineThe metabolism of Flunarizine can be decreased when combined with Pyrimethamine.
FlunitrazepamThe metabolism of Flunitrazepam can be decreased when combined with Pyrimethamine.
FluoxetineThe metabolism of Fluoxetine can be decreased when combined with Pyrimethamine.
FluphenazineThe serum concentration of Fluphenazine can be increased when it is combined with Pyrimethamine.
FlurbiprofenThe metabolism of Flurbiprofen can be decreased when combined with Pyrimethamine.
FluvastatinThe metabolism of Fluvastatin can be decreased when combined with Pyrimethamine.
FormoterolThe metabolism of Formoterol can be decreased when combined with Pyrimethamine.
FosphenytoinThe metabolism of Fosphenytoin can be decreased when combined with Pyrimethamine.
GavestinelThe metabolism of Gavestinel can be decreased when combined with Pyrimethamine.
GliclazideThe metabolism of Gliclazide can be decreased when combined with Pyrimethamine.
GlimepirideThe metabolism of Glimepiride can be decreased when combined with Pyrimethamine.
GlipizideThe metabolism of Glipizide can be decreased when combined with Pyrimethamine.
GlyburideThe metabolism of Glyburide can be decreased when combined with Pyrimethamine.
GuanfacineThe metabolism of Guanfacine can be decreased when combined with Pyrimethamine.
HaloperidolThe metabolism of Haloperidol can be decreased when combined with Pyrimethamine.
HalothaneThe metabolism of Halothane can be decreased when combined with Pyrimethamine.
HexobarbitalThe metabolism of Hexobarbital can be decreased when combined with Pyrimethamine.
Histamine PhosphateThe metabolism of Histamine Phosphate can be decreased when combined with Pyrimethamine.
HydromorphoneThe metabolism of Hydromorphone can be decreased when combined with Pyrimethamine.
IbuprofenThe metabolism of Ibuprofen can be decreased when combined with Pyrimethamine.
IdarubicinThe metabolism of Idarubicin can be decreased when combined with Pyrimethamine.
IfosfamideThe metabolism of Ifosfamide can be decreased when combined with Pyrimethamine.
ImatinibThe metabolism of Imatinib can be decreased when combined with Pyrimethamine.
indisulamThe metabolism of indisulam can be decreased when combined with Pyrimethamine.
IndomethacinThe metabolism of Indomethacin can be decreased when combined with Pyrimethamine.
IrbesartanThe metabolism of Irbesartan can be decreased when combined with Pyrimethamine.
IxazomibThe metabolism of Ixazomib can be decreased when combined with Pyrimethamine.
KetamineThe metabolism of Ketamine can be decreased when combined with Pyrimethamine.
KetobemidoneThe metabolism of Ketobemidone can be decreased when combined with Pyrimethamine.
KetoprofenThe metabolism of Ketoprofen can be decreased when combined with Pyrimethamine.
LansoprazoleThe metabolism of Lansoprazole can be decreased when combined with Pyrimethamine.
LeflunomideThe metabolism of Leflunomide can be decreased when combined with Pyrimethamine.
LesinuradThe metabolism of Lesinurad can be decreased when combined with Pyrimethamine.
LicofeloneThe metabolism of Licofelone can be decreased when combined with Pyrimethamine.
LidocaineThe metabolism of Lidocaine can be decreased when combined with Pyrimethamine.
LoratadineThe metabolism of Loratadine can be decreased when combined with Pyrimethamine.
LornoxicamThe metabolism of Lornoxicam can be decreased when combined with Pyrimethamine.
LosartanThe metabolism of Losartan can be decreased when combined with Pyrimethamine.
LumefantrineThe risk or severity of adverse effects can be increased when Pyrimethamine is combined with Lumefantrine.
LumiracoxibThe metabolism of Lumiracoxib can be decreased when combined with Pyrimethamine.
Mefenamic acidThe metabolism of Mefenamic acid can be decreased when combined with Pyrimethamine.
MelatoninThe metabolism of Melatonin can be decreased when combined with Pyrimethamine.
MeloxicamThe metabolism of Meloxicam can be decreased when combined with Pyrimethamine.
MephenytoinThe metabolism of Mephenytoin can be decreased when combined with Pyrimethamine.
MesoridazineThe serum concentration of Mesoridazine can be increased when it is combined with Pyrimethamine.
MestranolThe metabolism of Mestranol can be decreased when combined with Pyrimethamine.
MethadoneThe metabolism of Methadone can be decreased when combined with Pyrimethamine.
MethotrimeprazineThe serum concentration of Methotrimeprazine can be increased when it is combined with Pyrimethamine.
MethoxyfluraneThe metabolism of Methoxyflurane can be decreased when combined with Pyrimethamine.
Methylene blueThe serum concentration of Methylene blue can be increased when it is combined with Pyrimethamine.
MetoprololThe serum concentration of Metoprolol can be increased when it is combined with Pyrimethamine.
MetronidazoleThe metabolism of Metronidazole can be decreased when combined with Pyrimethamine.
MirtazapineThe metabolism of Mirtazapine can be decreased when combined with Pyrimethamine.
MoclobemideThe metabolism of Moclobemide can be decreased when combined with Pyrimethamine.
MontelukastThe metabolism of Montelukast can be decreased when combined with Pyrimethamine.
MoricizineThe serum concentration of Moricizine can be increased when it is combined with Pyrimethamine.
NaproxenThe metabolism of Naproxen can be decreased when combined with Pyrimethamine.
NateglinideThe metabolism of Nateglinide can be decreased when combined with Pyrimethamine.
NetupitantThe metabolism of Netupitant can be decreased when combined with Pyrimethamine.
NevirapineThe metabolism of Nevirapine can be decreased when combined with Pyrimethamine.
NiclosamideThe metabolism of Niclosamide can be decreased when combined with Pyrimethamine.
NicotineThe metabolism of Nicotine can be decreased when combined with Pyrimethamine.
NortriptylineThe metabolism of Nortriptyline can be decreased when combined with Pyrimethamine.
OlodaterolThe metabolism of Olodaterol can be decreased when combined with Pyrimethamine.
OmeprazoleThe metabolism of Omeprazole can be decreased when combined with Pyrimethamine.
OndansetronThe metabolism of Ondansetron can be decreased when combined with Pyrimethamine.
OspemifeneThe metabolism of Ospemifene can be decreased when combined with Pyrimethamine.
OxaprozinThe metabolism of Oxaprozin can be decreased when combined with Pyrimethamine.
PaclitaxelThe metabolism of Paclitaxel can be decreased when combined with Pyrimethamine.
ParamethadioneThe metabolism of Paramethadione can be decreased when combined with Pyrimethamine.
ParecoxibThe metabolism of Parecoxib can be decreased when combined with Pyrimethamine.
PerphenazineThe serum concentration of Perphenazine can be increased when it is combined with Pyrimethamine.
PhenacetinThe metabolism of Phenacetin can be decreased when combined with Pyrimethamine.
PhenobarbitalThe metabolism of Phenobarbital can be decreased when combined with Pyrimethamine.
PhenprocoumonThe metabolism of Phenprocoumon can be decreased when combined with Pyrimethamine.
PhenylbutazoneThe metabolism of Phenylbutazone can be decreased when combined with Pyrimethamine.
PhenytoinThe metabolism of Phenytoin can be decreased when combined with Pyrimethamine.
PioglitazoneThe metabolism of Pioglitazone can be decreased when combined with Pyrimethamine.
PiroxicamThe metabolism of Piroxicam can be decreased when combined with Pyrimethamine.
PitavastatinThe metabolism of Pitavastatin can be decreased when combined with Pyrimethamine.
PrasugrelThe metabolism of Prasugrel can be decreased when combined with Pyrimethamine.
PravastatinThe metabolism of Pravastatin can be decreased when combined with Pyrimethamine.
ProchlorperazineThe serum concentration of Prochlorperazine can be increased when it is combined with Pyrimethamine.
ProgesteroneThe metabolism of Progesterone can be decreased when combined with Pyrimethamine.
ProguanilThe metabolism of Proguanil can be decreased when combined with Pyrimethamine.
PromazineThe serum concentration of Promazine can be increased when it is combined with Pyrimethamine.
PromethazineThe serum concentration of Promethazine can be increased when it is combined with Pyrimethamine.
PropofolThe metabolism of Propofol can be decreased when combined with Pyrimethamine.
QuazepamThe metabolism of Quazepam can be decreased when combined with Pyrimethamine.
QuinidineThe metabolism of Quinidine can be decreased when combined with Pyrimethamine.
QuinineThe metabolism of Quinine can be decreased when combined with Pyrimethamine.
RifampicinThe metabolism of Rifampicin can be decreased when combined with Pyrimethamine.
RofecoxibThe metabolism of Rofecoxib can be decreased when combined with Pyrimethamine.
RosiglitazoneThe metabolism of Rosiglitazone can be decreased when combined with Pyrimethamine.
RosuvastatinThe metabolism of Rosuvastatin can be decreased when combined with Pyrimethamine.
Salicylic acidThe metabolism of Salicylic acid can be decreased when combined with Pyrimethamine.
SelegilineThe metabolism of Selegiline can be decreased when combined with Pyrimethamine.
SeratrodastThe metabolism of Seratrodast can be decreased when combined with Pyrimethamine.
SertralineThe metabolism of Sertraline can be decreased when combined with Pyrimethamine.
SildenafilThe metabolism of Sildenafil can be decreased when combined with Pyrimethamine.
SitaxentanThe metabolism of Sitaxentan can be decreased when combined with Pyrimethamine.
SulfadiazineThe metabolism of Sulfadiazine can be decreased when combined with Pyrimethamine.
SulfamethoxazoleThe metabolism of Sulfamethoxazole can be decreased when combined with Pyrimethamine.
SulfamoxoleThe metabolism of Sulfamoxole can be decreased when combined with Pyrimethamine.
SulfinpyrazoneThe metabolism of Sulfinpyrazone can be decreased when combined with Pyrimethamine.
SulfisoxazoleThe metabolism of Sulfisoxazole can be decreased when combined with Pyrimethamine.
SuprofenThe metabolism of Suprofen can be decreased when combined with Pyrimethamine.
TamoxifenThe metabolism of Tamoxifen can be decreased when combined with Pyrimethamine.
TapentadolThe metabolism of Tapentadol can be decreased when combined with Pyrimethamine.
TemazepamThe metabolism of Temazepam can be decreased when combined with Pyrimethamine.
TenoxicamThe metabolism of Tenoxicam can be decreased when combined with Pyrimethamine.
TerbinafineThe metabolism of Terbinafine can be decreased when combined with Pyrimethamine.
TerfenadineThe metabolism of Terfenadine can be decreased when combined with Pyrimethamine.
TestosteroneThe metabolism of Testosterone can be decreased when combined with Pyrimethamine.
ThalidomideThe metabolism of Thalidomide can be decreased when combined with Pyrimethamine.
TheophyllineThe metabolism of Theophylline can be decreased when combined with Pyrimethamine.
ThiamylalThe metabolism of Thiamylal can be decreased when combined with Pyrimethamine.
ThiethylperazineThe serum concentration of Thiethylperazine can be increased when it is combined with Pyrimethamine.
ThioridazineThe serum concentration of Thioridazine can be increased when it is combined with Pyrimethamine.
TolbutamideThe metabolism of Tolbutamide can be decreased when combined with Pyrimethamine.
TolterodineThe metabolism of Tolterodine can be decreased when combined with Pyrimethamine.
TorasemideThe metabolism of Torasemide can be decreased when combined with Pyrimethamine.
TrabectedinThe metabolism of Trabectedin can be decreased when combined with Pyrimethamine.
TreprostinilThe metabolism of Treprostinil can be decreased when combined with Pyrimethamine.
TretinoinThe metabolism of Tretinoin can be decreased when combined with Pyrimethamine.
TrifluoperazineThe serum concentration of Trifluoperazine can be increased when it is combined with Pyrimethamine.
TriflupromazineThe serum concentration of Triflupromazine can be increased when it is combined with Pyrimethamine.
TrimethadioneThe metabolism of Trimethadione can be decreased when combined with Pyrimethamine.
TrimethoprimThe metabolism of Trimethoprim can be decreased when combined with Pyrimethamine.
TrimipramineThe metabolism of Trimipramine can be decreased when combined with Pyrimethamine.
TroglitazoneThe metabolism of Troglitazone can be decreased when combined with Pyrimethamine.
ValdecoxibThe metabolism of Valdecoxib can be decreased when combined with Pyrimethamine.
Valproic AcidThe metabolism of Valproic Acid can be decreased when combined with Pyrimethamine.
ValsartanThe metabolism of Valsartan can be decreased when combined with Pyrimethamine.
VenlafaxineThe metabolism of Venlafaxine can be decreased when combined with Pyrimethamine.
VerapamilThe metabolism of Verapamil can be decreased when combined with Pyrimethamine.
VicrivirocThe metabolism of Vicriviroc can be decreased when combined with Pyrimethamine.
VismodegibThe metabolism of Vismodegib can be decreased when combined with Pyrimethamine.
VoriconazoleThe metabolism of Voriconazole can be decreased when combined with Pyrimethamine.
VortioxetineThe metabolism of Vortioxetine can be decreased when combined with Pyrimethamine.
WarfarinThe metabolism of Warfarin can be decreased when combined with Pyrimethamine.
XimelagatranThe metabolism of Ximelagatran can be decreased when combined with Pyrimethamine.
ZafirlukastThe metabolism of Zafirlukast can be decreased when combined with Pyrimethamine.
ZalcitabineThe metabolism of Zalcitabine can be decreased when combined with Pyrimethamine.
ZaltoprofenThe metabolism of Zaltoprofen can be decreased when combined with Pyrimethamine.
ZidovudineThe metabolism of Zidovudine can be decreased when combined with Pyrimethamine.
ZileutonThe metabolism of Zileuton can be decreased when combined with Pyrimethamine.
ZolpidemThe metabolism of Zolpidem can be decreased when combined with Pyrimethamine.
ZopicloneThe metabolism of Zopiclone can be decreased when combined with Pyrimethamine.
Food Interactions
  • Folic acid needs increased.
  • Take with food to reduce irritation.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Nadph binding
Specific Function:
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.
Gene Name:
DHFR
Uniprot ID:
P00374
Molecular Weight:
21452.61 Da
References
  1. Rastelli G, Pacchioni S, Parenti MD: Structure of Plasmodium vivax dihydrofolate reductase determined by homology modeling and molecular dynamics refinement. Bioorg Med Chem Lett. 2003 Oct 6;13(19):3257-60. [PubMed:12951104 ]
  2. Fidock DA, Wellems TE: Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect the intrinsic activity of proguanil. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10931-6. [PubMed:9380737 ]
  3. Wooden JM, Hartwell LH, Vasquez B, Sibley CH: Analysis in yeast of antimalaria drugs that target the dihydrofolate reductase of Plasmodium falciparum. Mol Biochem Parasitol. 1997 Mar;85(1):25-40. [PubMed:9108546 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Plasmodium falciparum (isolate K1 / Thailand)
Pharmacological action
yes
Actions
inhibitor
General Function:
Thymidylate synthase activity
Specific Function:
Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, DNA precursor synthesis, and for the conversion of dUMP to dTMP.
Gene Name:
Not Available
Uniprot ID:
P13922
Molecular Weight:
71816.775 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Fohl LM, Roos DS: Fitness effects of DHFR-TS mutations associated with pyrimethamine resistance in apicomplexan parasites. Mol Microbiol. 2003 Nov;50(4):1319-27. [PubMed:14622418 ]
  4. McKie JH, Douglas KT, Chan C, Roser SA, Yates R, Read M, Hyde JE, Dascombe MJ, Yuthavong Y, Sirawaraporn W: Rational drug design approach for overcoming drug resistance: application to pyrimethamine resistance in malaria. J Med Chem. 1998 Apr 23;41(9):1367-70. [PubMed:9554869 ]
  5. Zolg JW, Plitt JR, Chen GX, Palmer S: Point mutations in the dihydrofolate reductase-thymidylate synthase gene as the molecular basis for pyrimethamine resistance in Plasmodium falciparum. Mol Biochem Parasitol. 1989 Oct;36(3):253-62. [PubMed:2677719 ]
  6. Zhang K, Rathod PK: Divergent regulation of dihydrofolate reductase between malaria parasite and human host. Science. 2002 Apr 19;296(5567):545-7. [PubMed:11964483 ]

Enzymes

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
inhibitor
General Function:
Steroid 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. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 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:
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. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular Weight:
55824.275 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 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23