PYRIMETHAMINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H13ClN4
Molecular Weight	248.711
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCC1=NC(N)=NC(N)=C1C2=CC=C(Cl)C=C2

InChI

InChIKey=WKSAUQYGYAYLPV-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C12H13ClN4
Molecular Weight	248.711
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/9554869

Pyrimethamine, sold under the trade name Daraprim, is one of the folic acid antagonists that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis. In addition it was approved in Chemoprophylaxis of Malaria. However, resistance to pyrimethamine is prevalent worldwide. It is not suitable as a prophylactic agent for travelers to most areas. Pyrimethamine is well absorbed with peak levels occurring between 2 to 6 hours following administration. It is eliminated slowly and has a plasma half-life of approximately 96 hours. Pyrimethamine is 87% bound to human plasma proteins. Pyrimethamine acts by selectively inhibiting malarial dihydrofolate reductase-thymidylate synthase 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. The action of pyrimethamine against Toxoplasma gondii is greatly enhanced when used in conjunction with sulfonamides.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dihydrofolate reductase 61 Target ID: CHEMBL1939 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9554869	Inhibitor 8504		1.5 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Toxoplasmosis 13 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf	Curative	Approved 8583	DARAPRIM Approved Use Treatment of Toxoplasmosis: DARAPRIM is indicated for the treatment of toxoplasmosis when used conjointly with a sulfonamide, since synergism exists with this combination. Treatment of Acute Malaria: DARAPRIM is also indicated for the treatment of acute malaria. It should not be used alone to treat acute malaria. Fast-acting schizonticides such as chloroquine or quinine are indicated and preferable for the treatment of acute malaria. However, conjoint use of DARAPRIM with a sulfonamide (e.g., sulfadoxine) will initiate transmission control and suppression of susceptible strains of plasmodia. Chemoprophylaxis of Malaria: DARAPRIM is indicated for the chemoprophylaxis of malaria due to susceptible strains of plasmodia. However, resistance to pyrimethamine is prevalent worldwide. It is not suitable as a prophylactic agent for travelers to most areas. Launch Date 1953
Acute malaria 6 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf	Curative	Approved 8583	DARAPRIM Approved Use Treatment of Toxoplasmosis: DARAPRIM is indicated for the treatment of toxoplasmosis when used conjointly with a sulfonamide, since synergism exists with this combination. Treatment of Acute Malaria: DARAPRIM is also indicated for the treatment of acute malaria. It should not be used alone to treat acute malaria. Fast-acting schizonticides such as chloroquine or quinine are indicated and preferable for the treatment of acute malaria. However, conjoint use of DARAPRIM with a sulfonamide (e.g., sulfadoxine) will initiate transmission control and suppression of susceptible strains of plasmodia. Chemoprophylaxis of Malaria: DARAPRIM is indicated for the chemoprophylaxis of malaria due to susceptible strains of plasmodia. However, resistance to pyrimethamine is prevalent worldwide. It is not suitable as a prophylactic agent for travelers to most areas. Launch Date 1953
Malaria 96 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf	Preventing	Approved 8583	DARAPRIM Approved Use Treatment of Toxoplasmosis: DARAPRIM is indicated for the treatment of toxoplasmosis when used conjointly with a sulfonamide, since synergism exists with this combination. Treatment of Acute Malaria: DARAPRIM is also indicated for the treatment of acute malaria. It should not be used alone to treat acute malaria. Fast-acting schizonticides such as chloroquine or quinine are indicated and preferable for the treatment of acute malaria. However, conjoint use of DARAPRIM with a sulfonamide (e.g., sulfadoxine) will initiate transmission control and suppression of susceptible strains of plasmodia. Chemoprophylaxis of Malaria: DARAPRIM is indicated for the chemoprophylaxis of malaria due to susceptible strains of plasmodia. However, resistance to pyrimethamine is prevalent worldwide. It is not suitable as a prophylactic agent for travelers to most areas. Launch Date 1953

C_max

Value	Dose	Co-administered	Analyte	Population
2.059 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8726001	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Zidovudine	Zidovudine	PYRIMETHAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
502.9 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8726001	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Zidovudine	Zidovudine	PYRIMETHAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
96 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/8578s15lbl.pdf	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		PYRIMETHAMINE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
190.56 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8726001	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Zidovudine	Zidovudine	PYRIMETHAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
13% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/8578s15lbl.pdf	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		PYRIMETHAMINE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
1.625 g single, oral Overdose Dose: 1.625 g Route: oral Route: single Dose: 1.625 g Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1	healthy, 1 Health Status: healthy Age Group: 1 Sex: M Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1	Disc. AE: Vomiting, Convulsions... AEs leading to discontinuation/dose reduction: Vomiting Convulsions (severe) Cyanosis Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1
625 mg single, oral Overdose Dose: 625 mg Route: oral Route: single Dose: 625 mg Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1	healthy, 1 Health Status: healthy Age Group: 1 Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1	Disc. AE: Convulsions, Respiratory failure... AEs leading to discontinuation/dose reduction: Convulsions Respiratory failure (grade 5) Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1
1.2 g single, oral Overdose Dose: 1.2 g Route: oral Route: single Dose: 1.2 g Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1	healthy, 2 Health Status: healthy Age Group: 2 Sex: M Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1	Disc. AE: Cyanosis, Vomiting... AEs leading to discontinuation/dose reduction: Cyanosis Vomiting (severe) Convulsions Apnoea Haematemesis Cardiac failure (grade 5) Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1
400 mg single, oral Overdose Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1	healthy, 2 Health Status: healthy Age Group: 2 Sex: F Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1	Disc. AE: Convulsions, Vomiting... AEs leading to discontinuation/dose reduction: Convulsions (severe) Vomiting Cyanosis Collapse Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1
625 mg single, oral Overdose Dose: 625 mg Route: oral Route: single Dose: 625 mg Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1	healthy, 3 Health Status: healthy Age Group: 3 Sex: F Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1	Disc. AE: Convulsions, Unconsciousness... AEs leading to discontinuation/dose reduction: Convulsions (grade 5) Unconsciousness (grade 5) Sources: http://apps.who.int/iris/bitstream/handle/10665/65774/WHO_MAL_79.907.pdf?sequence=1
300 mg single, oral Overdose Dose: 300 mg Route: oral Route: single Dose: 300 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf	Disc. AE: Convulsions, Abdominal pain... AEs leading to discontinuation/dose reduction: Convulsions Abdominal pain Nausea Vomiting (severe) Excitability Respiratory depression (grade 5) Circulatory collapse (grade 5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf
75 mg 1 times / day multiple, oral Recommended Dose: 75 mg, 1 times / day Route: oral Route: multiple Dose: 75 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf	Disc. AE: Folate deficiency... AEs leading to discontinuation/dose reduction: Folate deficiency Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/08578slr016_daraprim_lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 activator 150	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 1057 CYP1A2 2153 CYP2C19 2057 ALDH1 41 MATE1 415 OCT1 620 OCT2 779 BSEP 550 OATP1B1 1079 OATP1B3 961	MRP5 41	CYP1A 59

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDM2In19	inconclusive [Activation 10 uM]
ALDH1 41	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNTc3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDM2In19	inconclusive [Activation 39.8107 uM]
CYP3A4 2633	activator 342 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMzYifX0%3D	inconclusive [Activation 5.0119 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMzYifX0%3D	inconclusive [Activation 7.9433 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMzYifX0%3D	inconclusive [Activation >10 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDM2In19	no [Activation >10 uM]
CYP1A 122	inducer 1966 Sources: https://pubmed.ncbi.nlm.nih.gov/12451431/	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDM2In19	no
BSEP 554	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22961681/	weak [IC50 200.1 uM]
MATE1 416	inhibitor 4027 Sources: https://go.drugbank.com/drugs/DB00205, https://pubmed.ncbi.nlm.nih.gov/28971610/	yes [IC50 0.131 uM]
OCT1 656	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/31427432/	yes [IC50 1.8 uM]
OCT2 782	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/28971610/	yes [IC50 4.55 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://go.drugbank.com/drugs/DB00205, https://pubmed.ncbi.nlm.nih.gov/26721703/	yes [IC50 45.1 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23571415/	yes
OATP1B3 970	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23571415/	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
MRP5 41	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/12869626/	no

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:8673	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:8673
ChemicalBook	CB8461315	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8461315
eMolecules	511729	https://www.emolecules.com/cgi-bin/more?vid=511729
MolPort	MolPort-001-783-655	https://www.molport.com/shop/molecule-link/MolPort-001-783-655
Selleck Chemicals	Pyrimethamine	http://www.selleckchem.com/products/Pyrimethamine.html
ZINC	ZINC000000057464	http://zinc15.docking.org/substances/ZINC000000057464

PubMed

Title	Date	PubMed
In vitro cultivation of Cryptosporidium parvum and screening for anticryptosporidial drugs.	1990 Aug	2221857
In vivo assessment of antimicrobial agents against Toxoplasma gondii by quantification of parasites in the blood, lungs, and brain of infected mice.	1990 Aug	2221854
Resolution of acute renal failure in toxoplasmic encephalitis despite continuance of sulfadiazine.	1990 Jul-Aug	2385768
In vitro and in vivo effects of doxycycline on Toxoplasma gondii.	1990 May	2360817
Evaluation of the effect of drugs on the cyst form of Toxoplasma gondii.	1991 Jul	1647421
Activity of minocycline against Toxoplasma gondii infection in mice.	1991 May	1885421
Sulfadiazine-induced crystalluria in AIDS patients with toxoplasma encephalitis.	1991 May	1863412
Synergistic activity of azithromycin and pyrimethamine or sulfadiazine in acute experimental toxoplasmosis.	1992 May	1324642
Antituberculosis activity of certain antifungal and antihelmintic drugs.	1999	10707260
Expression and characterization of recombinant human-derived Pneumocystis carinii dihydrofolate reductase.	2000 Nov	11036028
Inhibition of growth of Pneumocystis carinii by lactoferrins alone and in combination with pyrimethamine, clarithromycin and minocycline.	2000 Oct	11020255
Anti-toxoplasma activities of antiretroviral drugs and interactions with pyrimethamine and sulfadiazine in vitro.	2000 Sep	10952623
Activity of gatifloxacin alone or in combination with pyrimethamine or gamma interferon against Toxoplasma gondii.	2001 Jan	11120943
[Malaria vector control in Cameroon: past, present, future. Reflections].	2001 Jul	16579079
Synthesis of 2,4-diamino-6-(thioarylmethyl)pyrido[2,3-d]pyrimidines as dihydrofolate reductase inhibitors.	2001 Nov	11597474
Selection of drugs to test the specificity of the Tg.AC assay by screening for induction of the gadd153 promoter in vitro.	2003 Aug	12730611
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.	2004 Jan 15	14711307
Pyrimethamine (2,4-diamino-5-p-chlorophenyl-6-ethylpyrimidine) induces apoptosis of freshly isolated human T lymphocytes, bypassing CD95/Fas molecule but involving its intrinsic pathway.	2005 Dec	16157660
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Hydrogen-bonding patterns in pyrimethaminium dinitrate.	2005 Oct	16210764
Research influence on antimalarial drug policy change in Tanzania: case study of replacing chloroquine with sulfadoxine-pyrimethamine as the first-line drug.	2005 Oct 20	16242017
Sulfonamide crystals and acute renal failure.	2006 Jun	16732870
Presumed dapsone-induced drug hypersensitivity syndrome causing reversible hypersensitivity myocarditis and thyrotoxicosis.	2006 Nov	17160201
[Acute renal failure due to sulfadiazine crystalluria].	2007 May	17907889
Suppression of telomerase activity by pyrimethamine: implication to cancer.	2007 Oct	18392083
A comparison of vitamin A and leucovorin for the prevention of methotrexate-induced micronuclei production in rat bone marrow.	2008 Dec	19061007
Anti-toxoplasmosis effects of oleuropein isolated from Fraxinus rhychophylla.	2008 Dec	19043212
ECVAM retrospective validation of in vitro micronucleus test (MNT).	2008 Jul	18326866
Pyrimethamine induces apoptosis of melanoma cells via a caspase and cathepsin double-edged mechanism.	2008 Jul 1	18593930
Impact of placental Plasmodium falciparum malaria on pregnancy and perinatal outcome in sub-Saharan Africa: part III: placental malaria, maternal health, and public health.	2008 Mar	18604306
Changes in malaria indices between 1999 and 2007 in The Gambia: a retrospective analysis.	2008 Nov 1	18984187
HIV, TB, Malaria, Filaria and Kala azar.	2008 Oct	21593967
Cost effectiveness of seasonal intermittent preventive treatment using amodiaquine & artesunate or sulphadoxine-pyrimethamine in Ghanaian children.	2010 Aug 17	20808923
Structure-activity relationships of carbocyclic 6-benzylthioinosine analogues as subversive substrates of Toxoplasma gondii adenosine kinase.	2010 May 15	20456959
Evaluation of the effect of pyrimethamine, an anti-malarial drug, on HIV-1 replication.	2010 Nov	20800626
Pyrimethamine induces oxidative stress in Plasmodium yoelii 17XL-infected mice: a novel immunomodulatory mechanism of action for an old antimalarial drug?	2010 Nov	20193682
Toxoplasma gondii: inhibitory activity and encystation effect of securinine and pyrrolidine derivatives on Toxoplasma growth.	2011 Feb	20833168
Use of the NP-40 detergent-mediated assay in discovery of inhibitors of beta-hematin crystallization.	2011 Jul	21518844
Crystal structure of β-hexosaminidase B in complex with pyrimethamine, a potential pharmacological chaperone.	2011 Mar 10	21265544
Antiplasmodial and analgesic activities of Clausena anisata.	2012 Mar	22305787
Palmitate increases the susceptibility of cells to drug-induced toxicity: an in vitro method to identify drugs with potential contraindications in patients with metabolic disease.	2012 Oct	22700542
Malarial dihydrofolate reductase as a paradigm for drug development against a resistance-compromised target.	2012 Oct 16	23035243
Identification of a new chemical class of antimalarials.	2012 Sep 1	22732921
In vitro and in vivo characterization of the antimalarial lead compound SSJ-183 in Plasmodium models.	2013	24255594
A new protoberberine alkaloid from Meconopsis simplicifolia (D. Don) Walpers with potent antimalarial activity against a multidrug resistant Plasmodium falciparum strain.	2013 Dec 12	24120516
Synthesis, characterization and antimalarial activity of quinoline-pyrimidine hybrids.	2013 Jan 1	23168082
Male and female Plasmodium falciparum mature gametocytes show different responses to antimalarial drugs.	2013 Jul	23629698
Toxoplasma gondii: the effect of fluconazole combined with sulfadiazine and pyrimethamine against acute toxoplasmosis in murine model.	2013 Mar	23270807
A facile three-component [3+2]-cycloaddition for the regioselective synthesis of highly functionalised dispiropyrrolidines acting as antimycobacterial agents.	2013 Mar 1	23352268
Antimycobacterial activity of nitrogen heterocycles derivatives: bipyridine derivatives. Part III.	2014 Mar 3	24268596

Patents

Sample Use Guides

In Vivo Use Guide

Toxoplasmosis: The adult starting dose is 50 to 75 mg of the drug daily, together with 1 to 4 g daily of a sulfonamide of the sulfapyrimidine type, e.g., sulfadoxine. This dosage is ordinarily continued for 1 to 3 weeks, depending on the response of the patient and tolerance to therapy. The dosage may then be reduced to about one half that previously given for each drug and continued for an additional 4 to 5 weeks. The pediatric dosage of DARAPRIM (PYRIMETHAMINE) is 1 mg/kg/day divided into 2 equal daily doses; after 2 to 4 days this dose may be reduced to one half and continued for approximately 1 month. The usual pediatric sulfonamide dosage is used in conjunction with DARAPRIM. Treatment of Acute Malaria: at a dosage of 25 mg daily for 2 days with a sulfonamide will initiate transmission control and suppression of non-falciparum malaria. The adult dosage for acute malaria is 50 mg for 2 days; children 4 through 10 years old may be given 25 mg daily for 2 days. In any event, clinical cure should be followed by the once-weekly regimen described below for chemoprophylaxis. Regimens which include suppression should be extended through any characteristic periods of early recrudescence and late relapse, i.e., for at least 10 weeks in each case. For Chemoprophylaxis of Malaria: Adults and pediatric patients over 10 years — 25 mg (1 tablet) once weekly. Children 4 through 10 years — 12.5 mg (1/2 tablet) once weekly. Infants and children under 4 years — 6.25 mg (1/4 tablet) once weekly.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:55:01 GMT 2025` Edited by `admin` on `Mon Mar 31 17:55:01 GMT 2025`
Record UNII	Z3614QOX8W
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DARAPRIM

Preferred Name

English

PYRIMETHAMINE

Official Name

English

PYRIMETHAMINE [MART.]

Common Name

English

PYRIMETHAMINE [WHO-IP]

Common Name

English

FANSIDAR COMPONENT PYRIMETHAMINE

Common Name

English

RP-4753

Code

English

2,4-DIAMINO-5-(P-CHLOROPHENYL)-6-ETHYLPYRIMIDINE

Common Name

English

PYRIMETHAMINE [VANDF]

Common Name

English

CHLORIDINE

Common Name

English

Pyrimethamine [WHO-DD]

Common Name

English

WR-2978

Code

English

PYRIMETHAMINE [JAN]

Common Name

English

PYRIMETHAMINE [USP MONOGRAPH]

Common Name

English

PYRIMETHAMINE [IARC]

Common Name

English

pyrimethamine [INN]

Common Name

English

PYRIMETHAMINE [MI]

Common Name

English

PYRIMETHAMINE [GREEN BOOK]

Common Name

English

GNF-PF-5586

Code

English

TCMDC-125860

Code

English

PYRIMETHAMINE [EP MONOGRAPH]

Common Name

English

PYRIMETHAMINE [USP-RS]

Common Name

English

PYRIMETHAMINUM [WHO-IP LATIN]

Common Name

English

2,4-PYRIMIDINEDIAMINE, 5-(4-CHLOROPHENYL)-6-ETHYL-

Systematic Name

English

NSC-3061

Code

English

PYRIMETHAMINE [ORANGE BOOK]

Common Name

English

Classification Tree Code System Code

LIVERTOX

NBK548044