Identification
NamePyrimethamine
Accession NumberDB00205  (APRD00599)
TypeSmall Molecule
GroupsApproved, Vet Approved
Description

One 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 IDs NSC-3061 / RP-4753 / WR-2978
Product Ingredients
IngredientUNIICASInChI KeyDetails
Pyrimethamine HydrochlorideNot Available19085-09-7JZCLIFPQURTYFA-UHFFFAOYSA-NDetails
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DaraprimTablet25 mg/1OralKaiser Foundations Hospitals2011-04-20Not applicableUs
DaraprimTablet25 mgOralAmedra Pharmaceuticals LLC1952-12-312013-06-01Canada
DaraprimTablet25 mg/1OralAmedra Pharmaceuticals LLC1953-01-23Not applicableUs
DaraprimTablet25 mg/1OralTuring Pharmaceuticals1953-01-23Not applicableUs
DaraprimTablet25 mg/1OralRemedy Repack2013-02-262016-10-13Us
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
Pyrimethamine LeucovorinSouth Coast Specialty Compounding, Inc. D/B/A Park Compounding
Categories
UNIIZ3614QOX8W
CAS number58-14-0
WeightAverage: 248.711
Monoisotopic: 248.082874143
Chemical FormulaC12H13ClN4
InChI KeyWKSAUQYGYAYLPV-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
Pharmacology
Indication

For the treatment of toxoplasmosis and acute malaria; For the prevention of malaria in areas non-resistant to pyrimethamine

Structured Indications
Pharmacodynamics

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.

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.

TargetKindPharmacological actionActionsOrganismUniProt ID
Dihydrofolate reductaseProteinyes
inhibitor
HumanP00374 details
Bifunctional dihydrofolate reductase-thymidylate synthaseProteinyes
inhibitor
Plasmodium falciparum (isolate K1 / Thailand)P13922 details
Beta-hexosaminidase subunit betaProteinunknownNot AvailableHumanP07686 details
Related Articles
Absorption

Well absorbed with peak levels occurring between 2 to 6 hours following administration

Volume of distributionNot Available
Protein binding

87%

Metabolism

Hepatic

Route of eliminationNot Available
Half life

96 hours

ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Plasmodium
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AceclofenacThe metabolism of Aceclofenac can be decreased when combined with Pyrimethamine.Approved
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Pyrimethamine.Approved
AcepromazineThe serum concentration of Acepromazine can be increased when it is combined with Pyrimethamine.Approved, Vet Approved
AceprometazineThe serum concentration of Aceprometazine can be increased when it is combined with Pyrimethamine.Approved
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Pyrimethamine.Approved
Acetylsalicylic acidThe metabolism of Acetylsalicylic acid can be decreased when combined with Pyrimethamine.Approved, Vet Approved
AlimemazineThe serum concentration of Alimemazine can be increased when it is combined with Pyrimethamine.Approved, Vet Approved
AlosetronThe metabolism of Alosetron can be decreased when combined with Pyrimethamine.Approved, Withdrawn
AlprazolamThe metabolism of Alprazolam can be decreased when combined with Pyrimethamine.Approved, Illicit, Investigational
AminophenazoneThe metabolism of Aminophenazone can be decreased when combined with Pyrimethamine.Approved, Withdrawn
AmiodaroneThe metabolism of Amiodarone can be decreased when combined with Pyrimethamine.Approved, Investigational
AmitriptylineThe metabolism of Amitriptyline can be decreased when combined with Pyrimethamine.Approved
AmodiaquineThe serum concentration of Amodiaquine can be increased when it is combined with Pyrimethamine.Approved
AmprenavirThe metabolism of Amprenavir can be decreased when combined with Pyrimethamine.Approved
AntipyrineThe metabolism of Antipyrine can be decreased when combined with Pyrimethamine.Approved
ApixabanThe metabolism of Apixaban can be decreased when combined with Pyrimethamine.Approved
Arachidonic AcidThe metabolism of Arachidonic Acid can be decreased when combined with Pyrimethamine.Experimental
ArformoterolThe metabolism of Arformoterol can be decreased when combined with Pyrimethamine.Approved, Investigational
ArtemetherThe risk or severity of adverse effects can be increased when Artemether is combined with Pyrimethamine.Approved
AtazanavirThe metabolism of Atazanavir can be decreased when combined with Pyrimethamine.Approved, Investigational
AzelastineThe metabolism of Azelastine can be decreased when combined with Pyrimethamine.Approved
BexaroteneThe metabolism of Bexarotene can be decreased when combined with Pyrimethamine.Approved, Investigational
BL-1020The serum concentration of BL-1020 can be increased when it is combined with Pyrimethamine.Investigational
BortezomibThe metabolism of Bortezomib can be decreased when combined with Pyrimethamine.Approved, Investigational
BosentanThe serum concentration of Bosentan can be increased when it is combined with Pyrimethamine.Approved, Investigational
BrompheniramineThe metabolism of Brompheniramine can be decreased when combined with Pyrimethamine.Approved
BuprenorphineThe metabolism of Buprenorphine can be decreased when combined with Pyrimethamine.Approved, Illicit, Investigational, Vet Approved
BupropionThe metabolism of Bupropion can be decreased when combined with Pyrimethamine.Approved
CabozantinibThe metabolism of Cabozantinib can be decreased when combined with Pyrimethamine.Approved
CaffeineThe metabolism of Caffeine can be decreased when combined with Pyrimethamine.Approved
CandesartanThe metabolism of Candesartan can be decreased when combined with Pyrimethamine.Approved
CarbinoxamineThe metabolism of Carbinoxamine can be decreased when combined with Pyrimethamine.Approved
CarvedilolThe serum concentration of Carvedilol can be increased when it is combined with Pyrimethamine.Approved, Investigational
CelecoxibThe metabolism of Celecoxib can be decreased when combined with Pyrimethamine.Approved, Investigational
ChlorpromazineThe serum concentration of Chlorpromazine can be increased when it is combined with Pyrimethamine.Approved, Vet Approved
ChlorpropamideThe metabolism of Chlorpropamide can be decreased when combined with Pyrimethamine.Approved
CinnarizineThe metabolism of Cinnarizine can be decreased when combined with Pyrimethamine.Approved
CisaprideThe metabolism of Cisapride can be decreased when combined with Pyrimethamine.Approved, Investigational, Withdrawn
ClopidogrelThe metabolism of Clopidogrel can be decreased when combined with Pyrimethamine.Approved, Nutraceutical
ClozapineThe metabolism of Clozapine can be decreased when combined with Pyrimethamine.Approved
CyclophosphamideThe metabolism of Cyclophosphamide can be decreased when combined with Pyrimethamine.Approved, Investigational
DapagliflozinThe metabolism of Dapagliflozin can be decreased when combined with Pyrimethamine.Approved
DapsoneThe risk or severity of adverse effects can be increased when Pyrimethamine is combined with Dapsone.Approved, Investigational
DapsoneThe metabolism of Dapsone can be decreased when combined with Pyrimethamine.Approved, Investigational
DextromethorphanThe metabolism of Dextromethorphan can be decreased when combined with Pyrimethamine.Approved
DiazepamThe metabolism of Diazepam can be decreased when combined with Pyrimethamine.Approved, Illicit, Vet Approved
DiclofenacThe metabolism of Diclofenac can be decreased when combined with Pyrimethamine.Approved, Vet Approved
DicoumarolThe metabolism of Dicoumarol can be decreased when combined with Pyrimethamine.Approved
DiltiazemThe metabolism of Diltiazem can be decreased when combined with Pyrimethamine.Approved
DiphenhydramineThe metabolism of Diphenhydramine can be decreased when combined with Pyrimethamine.Approved
DolasetronThe metabolism of Dolasetron can be decreased when combined with Pyrimethamine.Approved
DonepezilThe metabolism of Donepezil can be decreased when combined with Pyrimethamine.Approved
DopamineThe metabolism of Dopamine can be decreased when combined with Pyrimethamine.Approved
DorzolamideThe metabolism of Dorzolamide can be decreased when combined with Pyrimethamine.Approved
DoxepinThe metabolism of Doxepin can be decreased when combined with Pyrimethamine.Approved
DronabinolThe serum concentration of Dronabinol can be increased when it is combined with Pyrimethamine.Approved, Illicit
EletriptanThe metabolism of Eletriptan can be decreased when combined with Pyrimethamine.Approved, Investigational
EpoprostenolThe metabolism of Epoprostenol can be decreased when combined with Pyrimethamine.Approved
EstradiolThe metabolism of Estradiol can be decreased when combined with Pyrimethamine.Approved, Investigational, Vet Approved
EstroneThe metabolism of Estrone can be decreased when combined with Pyrimethamine.Approved
EszopicloneThe metabolism of Eszopiclone can be decreased when combined with Pyrimethamine.Approved
EtodolacThe metabolism of Etodolac can be decreased when combined with Pyrimethamine.Approved, Investigational, Vet Approved
EtoricoxibThe metabolism of Etoricoxib can be decreased when combined with Pyrimethamine.Approved, Investigational
EtravirineThe metabolism of Etravirine can be decreased when combined with Pyrimethamine.Approved
FesoterodineThe serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Pyrimethamine.Approved
FlunarizineThe metabolism of Flunarizine can be decreased when combined with Pyrimethamine.Approved
FlunitrazepamThe metabolism of Flunitrazepam can be decreased when combined with Pyrimethamine.Approved, Illicit
FluoxetineThe metabolism of Fluoxetine can be decreased when combined with Pyrimethamine.Approved, Vet Approved
FluphenazineThe serum concentration of Fluphenazine can be increased when it is combined with Pyrimethamine.Approved
FlurbiprofenThe metabolism of Flurbiprofen can be decreased when combined with Pyrimethamine.Approved, Investigational
FluvastatinThe metabolism of Fluvastatin can be decreased when combined with Pyrimethamine.Approved
FormoterolThe metabolism of Formoterol can be decreased when combined with Pyrimethamine.Approved, Investigational
FosphenytoinThe metabolism of Fosphenytoin can be decreased when combined with Pyrimethamine.Approved
GavestinelThe metabolism of Gavestinel can be decreased when combined with Pyrimethamine.Investigational
GliclazideThe metabolism of Gliclazide can be decreased when combined with Pyrimethamine.Approved
GlimepirideThe metabolism of Glimepiride can be decreased when combined with Pyrimethamine.Approved
GlipizideThe metabolism of Glipizide can be decreased when combined with Pyrimethamine.Approved
GlyburideThe metabolism of Glyburide can be decreased when combined with Pyrimethamine.Approved
GuanfacineThe metabolism of Guanfacine can be decreased when combined with Pyrimethamine.Approved, Investigational
HaloperidolThe metabolism of Haloperidol can be decreased when combined with Pyrimethamine.Approved
HalothaneThe metabolism of Halothane can be decreased when combined with Pyrimethamine.Approved, Vet Approved
HexobarbitalThe metabolism of Hexobarbital can be decreased when combined with Pyrimethamine.Approved
HistamineThe metabolism of Histamine Phosphate can be decreased when combined with Pyrimethamine.Approved, Investigational
HydromorphoneThe metabolism of Hydromorphone can be decreased when combined with Pyrimethamine.Approved, Illicit
IbuprofenThe metabolism of Ibuprofen can be decreased when combined with Pyrimethamine.Approved
IdarubicinThe metabolism of Idarubicin can be decreased when combined with Pyrimethamine.Approved
IfosfamideThe metabolism of Ifosfamide can be decreased when combined with Pyrimethamine.Approved
ImatinibThe metabolism of Imatinib can be decreased when combined with Pyrimethamine.Approved
IndomethacinThe metabolism of Indomethacin can be decreased when combined with Pyrimethamine.Approved, Investigational
IrbesartanThe metabolism of Irbesartan can be decreased when combined with Pyrimethamine.Approved, Investigational
IxazomibThe metabolism of Ixazomib can be decreased when combined with Pyrimethamine.Approved
KetamineThe metabolism of Ketamine can be decreased when combined with Pyrimethamine.Approved, Vet Approved
KetobemidoneThe metabolism of Ketobemidone can be decreased when combined with Pyrimethamine.Approved
KetoprofenThe metabolism of Ketoprofen can be decreased when combined with Pyrimethamine.Approved, Vet Approved
LansoprazoleThe metabolism of Lansoprazole can be decreased when combined with Pyrimethamine.Approved, Investigational
LeflunomideThe metabolism of Leflunomide can be decreased when combined with Pyrimethamine.Approved, Investigational
LesinuradThe metabolism of Lesinurad can be decreased when combined with Pyrimethamine.Approved
Levomefolic acidThe therapeutic efficacy of Pyrimethamine can be decreased when used in combination with Levomefolic acid.Approved
LicofeloneThe metabolism of Licofelone can be decreased when combined with Pyrimethamine.Investigational
LidocaineThe metabolism of Lidocaine can be decreased when combined with Pyrimethamine.Approved, Vet Approved
LoratadineThe metabolism of Loratadine can be decreased when combined with Pyrimethamine.Approved
LornoxicamThe metabolism of Lornoxicam can be decreased when combined with Pyrimethamine.Approved
LosartanThe metabolism of Losartan can be decreased when combined with Pyrimethamine.Approved
LumefantrineThe risk or severity of adverse effects can be increased when Pyrimethamine is combined with Lumefantrine.Approved
LumiracoxibThe metabolism of Lumiracoxib can be decreased when combined with Pyrimethamine.Approved, Investigational
Mefenamic acidThe metabolism of Mefenamic acid can be decreased when combined with Pyrimethamine.Approved
MelatoninThe metabolism of Melatonin can be decreased when combined with Pyrimethamine.Approved, Nutraceutical, Vet Approved
MeloxicamThe metabolism of Meloxicam can be decreased when combined with Pyrimethamine.Approved, Vet Approved
MephenytoinThe metabolism of Mephenytoin can be decreased when combined with Pyrimethamine.Investigational, Withdrawn
MesoridazineThe serum concentration of Mesoridazine can be increased when it is combined with Pyrimethamine.Approved
MestranolThe metabolism of Mestranol can be decreased when combined with Pyrimethamine.Approved
MethadoneThe metabolism of Methadone can be decreased when combined with Pyrimethamine.Approved
MethotrimeprazineThe serum concentration of Methotrimeprazine can be increased when it is combined with Pyrimethamine.Approved
MethoxyfluraneThe metabolism of Methoxyflurane can be decreased when combined with Pyrimethamine.Approved, Vet Approved
Methylene blueThe serum concentration of Methylene blue can be increased when it is combined with Pyrimethamine.Investigational
MetoprololThe serum concentration of Metoprolol can be increased when it is combined with Pyrimethamine.Approved, Investigational
MetronidazoleThe metabolism of Metronidazole can be decreased when combined with Pyrimethamine.Approved
MirtazapineThe metabolism of Mirtazapine can be decreased when combined with Pyrimethamine.Approved
MoclobemideThe metabolism of Moclobemide can be decreased when combined with Pyrimethamine.Approved
MontelukastThe metabolism of Montelukast can be decreased when combined with Pyrimethamine.Approved
MoricizineThe serum concentration of Moricizine can be increased when it is combined with Pyrimethamine.Approved, Withdrawn
NaproxenThe metabolism of Naproxen can be decreased when combined with Pyrimethamine.Approved, Vet Approved
NateglinideThe metabolism of Nateglinide can be decreased when combined with Pyrimethamine.Approved, Investigational
NetupitantThe metabolism of Netupitant can be decreased when combined with Pyrimethamine.Approved
NevirapineThe metabolism of Nevirapine can be decreased when combined with Pyrimethamine.Approved
NiclosamideThe metabolism of Niclosamide can be decreased when combined with Pyrimethamine.Approved, Vet Approved
NicotineThe metabolism of Nicotine can be decreased when combined with Pyrimethamine.Approved
NortriptylineThe metabolism of Nortriptyline can be decreased when combined with Pyrimethamine.Approved
OlodaterolThe metabolism of Olodaterol can be decreased when combined with Pyrimethamine.Approved
OmeprazoleThe metabolism of Omeprazole can be decreased when combined with Pyrimethamine.Approved, Investigational, Vet Approved
OndansetronThe metabolism of Ondansetron can be decreased when combined with Pyrimethamine.Approved
OspemifeneThe metabolism of Ospemifene can be decreased when combined with Pyrimethamine.Approved
OxaprozinThe metabolism of Oxaprozin can be decreased when combined with Pyrimethamine.Approved
PaclitaxelThe metabolism of Paclitaxel can be decreased when combined with Pyrimethamine.Approved, Vet Approved
ParamethadioneThe metabolism of Paramethadione can be decreased when combined with Pyrimethamine.Approved
ParecoxibThe metabolism of Parecoxib can be decreased when combined with Pyrimethamine.Approved
PerazineThe serum concentration of Perazine can be increased when it is combined with Pyrimethamine.Investigational
PerphenazineThe serum concentration of Perphenazine can be increased when it is combined with Pyrimethamine.Approved
PhenacetinThe metabolism of Phenacetin can be decreased when combined with Pyrimethamine.Withdrawn
PhenobarbitalThe metabolism of Phenobarbital can be decreased when combined with Pyrimethamine.Approved
PhenprocoumonThe metabolism of Phenprocoumon can be decreased when combined with Pyrimethamine.Approved
PhenylbutazoneThe metabolism of Phenylbutazone can be decreased when combined with Pyrimethamine.Approved, Vet Approved
PhenytoinThe metabolism of Phenytoin can be decreased when combined with Pyrimethamine.Approved, Vet Approved
PioglitazoneThe metabolism of Pioglitazone can be decreased when combined with Pyrimethamine.Approved, Investigational
PiroxicamThe metabolism of Piroxicam can be decreased when combined with Pyrimethamine.Approved, Investigational
PitavastatinThe metabolism of Pitavastatin can be decreased when combined with Pyrimethamine.Approved
PrasugrelThe metabolism of Prasugrel can be decreased when combined with Pyrimethamine.Approved
PravastatinThe metabolism of Pravastatin can be decreased when combined with Pyrimethamine.Approved
ProchlorperazineThe serum concentration of Prochlorperazine can be increased when it is combined with Pyrimethamine.Approved, Vet Approved
ProgesteroneThe metabolism of Progesterone can be decreased when combined with Pyrimethamine.Approved, Vet Approved
ProguanilThe metabolism of Proguanil can be decreased when combined with Pyrimethamine.Approved
PromazineThe serum concentration of Promazine can be increased when it is combined with Pyrimethamine.Approved, Vet Approved
PromethazineThe serum concentration of Promethazine can be increased when it is combined with Pyrimethamine.Approved
PropofolThe metabolism of Propofol can be decreased when combined with Pyrimethamine.Approved, Investigational, Vet Approved
QuazepamThe metabolism of Quazepam can be decreased when combined with Pyrimethamine.Approved, Illicit
QuinidineThe metabolism of Quinidine can be decreased when combined with Pyrimethamine.Approved
QuinineThe metabolism of Quinine can be decreased when combined with Pyrimethamine.Approved
RifampicinThe metabolism of Rifampicin can be decreased when combined with Pyrimethamine.Approved
RofecoxibThe metabolism of Rofecoxib can be decreased when combined with Pyrimethamine.Investigational, Withdrawn
RosiglitazoneThe metabolism of Rosiglitazone can be decreased when combined with Pyrimethamine.Approved, Investigational
RosuvastatinThe metabolism of Rosuvastatin can be decreased when combined with Pyrimethamine.Approved
Salicylic acidThe metabolism of Salicylic acid can be decreased when combined with Pyrimethamine.Approved, Vet Approved
SelegilineThe metabolism of Selegiline can be decreased when combined with Pyrimethamine.Approved, Investigational, Vet Approved
SertralineThe metabolism of Sertraline can be decreased when combined with Pyrimethamine.Approved
SildenafilThe metabolism of Sildenafil can be decreased when combined with Pyrimethamine.Approved, Investigational
SitaxentanThe metabolism of Sitaxentan can be decreased when combined with Pyrimethamine.Approved, Investigational, Withdrawn
SulfadiazineThe metabolism of Sulfadiazine can be decreased when combined with Pyrimethamine.Approved, Vet Approved
SulfamethoxazoleThe metabolism of Sulfamethoxazole can be decreased when combined with Pyrimethamine.Approved
SulfamoxoleThe metabolism of Sulfamoxole can be decreased when combined with Pyrimethamine.Approved
SulfinpyrazoneThe metabolism of Sulfinpyrazone can be decreased when combined with Pyrimethamine.Approved
SulfisoxazoleThe metabolism of Sulfisoxazole can be decreased when combined with Pyrimethamine.Approved, Vet Approved
SuprofenThe metabolism of Suprofen can be decreased when combined with Pyrimethamine.Approved, Withdrawn
TamoxifenThe metabolism of Tamoxifen can be decreased when combined with Pyrimethamine.Approved
TapentadolThe metabolism of Tapentadol can be decreased when combined with Pyrimethamine.Approved
TemazepamThe metabolism of Temazepam can be decreased when combined with Pyrimethamine.Approved
TenoxicamThe metabolism of Tenoxicam can be decreased when combined with Pyrimethamine.Approved
TerbinafineThe metabolism of Terbinafine can be decreased when combined with Pyrimethamine.Approved, Investigational, Vet Approved
TerfenadineThe metabolism of Terfenadine can be decreased when combined with Pyrimethamine.Withdrawn
TestosteroneThe metabolism of Testosterone can be decreased when combined with Pyrimethamine.Approved, Investigational
ThalidomideThe metabolism of Thalidomide can be decreased when combined with Pyrimethamine.Approved, Investigational, Withdrawn
TheophyllineThe metabolism of Theophylline can be decreased when combined with Pyrimethamine.Approved
ThiamylalThe metabolism of Thiamylal can be decreased when combined with Pyrimethamine.Approved, Vet Approved
ThiethylperazineThe serum concentration of Thiethylperazine can be increased when it is combined with Pyrimethamine.Withdrawn
ThioridazineThe serum concentration of Thioridazine can be increased when it is combined with Pyrimethamine.Withdrawn
TolbutamideThe metabolism of Tolbutamide can be decreased when combined with Pyrimethamine.Approved
TolterodineThe metabolism of Tolterodine can be decreased when combined with Pyrimethamine.Approved, Investigational
TorasemideThe metabolism of Torasemide can be decreased when combined with Pyrimethamine.Approved
TrabectedinThe metabolism of Trabectedin can be decreased when combined with Pyrimethamine.Approved, Investigational
TreprostinilThe metabolism of Treprostinil can be decreased when combined with Pyrimethamine.Approved, Investigational
TretinoinThe metabolism of Tretinoin can be decreased when combined with Pyrimethamine.Approved, Investigational, Nutraceutical
TrifluoperazineThe serum concentration of Trifluoperazine can be increased when it is combined with Pyrimethamine.Approved
TriflupromazineThe serum concentration of Triflupromazine can be increased when it is combined with Pyrimethamine.Approved, Vet Approved
TrimethadioneThe metabolism of Trimethadione can be decreased when combined with Pyrimethamine.Approved
TrimethoprimThe metabolism of Trimethoprim can be decreased when combined with Pyrimethamine.Approved, Vet Approved
TrimipramineThe metabolism of Trimipramine can be decreased when combined with Pyrimethamine.Approved
TroglitazoneThe metabolism of Troglitazone can be decreased when combined with Pyrimethamine.Withdrawn
ValdecoxibThe metabolism of Valdecoxib can be decreased when combined with Pyrimethamine.Investigational, Withdrawn
Valproic AcidThe metabolism of Valproic Acid can be decreased when combined with Pyrimethamine.Approved, Investigational
ValsartanThe metabolism of Valsartan can be decreased when combined with Pyrimethamine.Approved, Investigational
VenlafaxineThe metabolism of Venlafaxine can be decreased when combined with Pyrimethamine.Approved
VerapamilThe metabolism of Verapamil can be decreased when combined with Pyrimethamine.Approved
VismodegibThe metabolism of Vismodegib can be decreased when combined with Pyrimethamine.Approved
VoriconazoleThe metabolism of Voriconazole can be decreased when combined with Pyrimethamine.Approved, Investigational
VortioxetineThe metabolism of Vortioxetine can be decreased when combined with Pyrimethamine.Approved
WarfarinThe metabolism of Warfarin can be decreased when combined with Pyrimethamine.Approved
XimelagatranThe metabolism of Ximelagatran can be decreased when combined with Pyrimethamine.Approved, Investigational, Withdrawn
ZafirlukastThe metabolism of Zafirlukast can be decreased when combined with Pyrimethamine.Approved, Investigational
ZalcitabineThe metabolism of Zalcitabine can be decreased when combined with Pyrimethamine.Approved
ZaltoprofenThe metabolism of Zaltoprofen can be decreased when combined with Pyrimethamine.Approved
ZidovudineThe metabolism of Zidovudine can be decreased when combined with Pyrimethamine.Approved
ZileutonThe metabolism of Zileuton can be decreased when combined with Pyrimethamine.Approved, Investigational, Withdrawn
ZolpidemThe metabolism of Zolpidem can be decreased when combined with Pyrimethamine.Approved
ZopicloneThe metabolism of Zopiclone can be decreased when combined with Pyrimethamine.Approved
Food Interactions
  • Folic acid needs increased.
  • Take with food to reduce irritation.
References
Synthesis ReferenceUS2576939
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 CodesP01BF04 — Artesunate, sulphamethopyrazine and pyrimethamineP01BD01 — PyrimethamineP01BD51 — Pyrimethamine, combinations
AHFS Codes
  • 08:30.08
PDB Entries
FDA labelDownload (29.7 KB)
MSDSDownload (74 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedPreventionPlasmodium Infections1
1CompletedTreatmentAutoimmune Diseases / Lymphatic Diseases / Lymphoproliferative Disorders1
1CompletedTreatmentAutoimmune Diseases / Lymphoproliferative Disorders1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Toxoplasmosis, Cerebral2
1Not Yet RecruitingTreatmentMyelodysplastic Syndromes1
1RecruitingPreventionPlasmodium Infections1
1WithdrawnNot AvailableG(M2) Ganglioside / Sandhoff Disease Ganglioside / Tay-Sachs Disease Ganglioside1
1, 2CompletedTreatmentFamilial Amyotrophic Lateral Sclerosis1
1, 2CompletedTreatmentGangliosidoses, GM2 / Sandhoff Disease / Tay-Sachs Disease1
1, 2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemia, Small Lymphocytic1
2CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections / Toxoplasmosis, Cerebral1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Toxoplasmosis, Cerebral1
2, 3CompletedPreventionPlasmodium Infections1
2, 3CompletedTreatmentPlasmodium Infections1
3CompletedPreventionPlasmodium Infections1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Pneumonia, Pneumocystis Carinii1
3CompletedTreatmentMajor Depressive Disorder (MDD) / Schizophrenic Disorders1
3CompletedTreatmentPlasmodium Infections1
3CompletedTreatmentSchistosoma Mansoni1
3CompletedTreatmentToxoplasmosis, Congenital1
3RecruitingPreventionPlasmodium Infections / Pregnancy1
3TerminatedTreatmentPlasmodium Infections1
3WithdrawnTreatmentPlasmodium Falciparum Malaria1
4CompletedPreventionPlasmodium Infections1
4CompletedTreatmentPlasmodium Falciparum Malaria / Plasmodium Infections1
4RecruitingTreatmentToxoplasmosis1
Not AvailableCompletedPreventionHuman Immunodeficiency Virus (HIV) Infections / Toxoplasmosis, Cerebral1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Toxoplasmosis, Cerebral2
Not AvailableCompletedTreatmentMalaria caused by Plasmodium falciparum / Malaria caused by plasmodium vivax1
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 point (°C)233.5 °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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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 )
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0002-0090000000-a146b85d59fc9835ed4cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0002-0090000000-84e4cea277c64351f21bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0002-0190000000-d931593de00f33f04587View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0059-0980000000-a232e355dd50976aea07View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-005a-0920000000-7d48f7cfecbd7823803aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0002-0290000000-b6d3f56ade24c0e6984cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0002-0290000000-415b60a9caab352df184View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0032-2960000000-583d00b81182f34e5a94View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , PositiveNot Available
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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as aminopyrimidines and derivatives. These are organic compounds containing an amino group attached to a pyrimidine ring. 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 ParentAminopyrimidines and derivatives
Alternative ParentsChlorobenzenes / Hydropyrimidines / Aryl chlorides / Heteroaromatic compounds / Azacyclic compounds / Primary amines / Organopnictogen compounds / Organochlorides / Hydrocarbon derivatives
SubstituentsAminopyrimidine / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / Monocyclic benzene moiety / Hydropyrimidine / Benzenoid / Heteroaromatic compound / Azacycle
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptorsaminopyrimidine, monochlorobenzenes (CHEBI:8673 )

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
Uniprot Name:
Dihydrofolate reductase
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
Uniprot Name:
Bifunctional dihydrofolate reductase-thymidylate synthase
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Protein homodimerization activity
Specific Function:
Responsible for the degradation of GM2 gangliosides, and a variety of other molecules containing terminal N-acetyl hexosamines, in the brain and other tissues.
Gene Name:
HEXB
Uniprot ID:
P07686
Uniprot Name:
Beta-hexosaminidase subunit beta
Molecular Weight:
63110.745 Da
References
  1. Bateman KS, Cherney MM, Mahuran DJ, Tropak M, James MN: Crystal structure of beta-hexosaminidase B in complex with pyrimethamine, a potential pharmacological chaperone. J Med Chem. 2011 Mar 10;54(5):1421-9. doi: 10.1021/jm101443u. Epub 2011 Jan 25. [PubMed:21265544 ]

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
Uniprot Name:
Cytochrome P450 2D6
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
Uniprot Name:
Cytochrome P450 2C9
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
Uniprot Name:
Cytochrome P450 2C8
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 ]
Drug created on June 13, 2005 07:24 / Updated on July 18, 2017 16:46