Proguanil

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Proguanil
Proguanil.svg
Systematic (IUPAC) name
1-[amino-(4-chloroanilino)methylidene]-2-propan-2-ylguanidine
Clinical data
Trade names Paludrine
AHFS/Drugs.com Micromedex Detailed Consumer Information
Routes of
administration
By mouth (tablets)
Legal status
Legal status
  • ℞ (Prescription only)
Pharmacokinetic data
Protein binding 75%
Metabolism By liver (CYP2C19)
Metabolites cycloguanil and 4-chlorophenylbiguanide
Biological half-life 12–21 hours[1]
Identifiers
CAS Number 500-92-5 YesY
ATC code P01BB01 (WHO)
PubChem CID 4923
DrugBank DB01131 YesY
ChemSpider 4754 YesY
UNII S61K3P7B2V YesY
KEGG D08428 YesY
ChEBI CHEBI:8455 YesY
ChEMBL CHEMBL1377 YesY
Chemical data
Formula C11H16ClN5
Molar mass 253.731 g/mol
  (verify)

Proguanil (also known as chlorguanide and chloroguanide) is a prophylactic antimalarial drug. When taken, it is converted to the active metabolite cycloguanil.[2][3] Proguanil is effective against sporozoites. Proguanil hydrochloride is marketed as Paludrine by AstraZeneca.

It has been used for malarial prophylaxis in children with sickle-cell disease living in malaria-endemic areas for many years.

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[4]

Medical uses[edit]

Proguanil is usually taken in combination with another antimalarial drug, such as atovaquone[5] or chloroquine.[6]

Atovaquone/proguanil has fewer side effects than mefloquine, but can be more expensive because it is taken daily.

Proguanil is taken with atovaquone for chloroquine-resistant and multidrug resistant strains of P. falciparum and P. vivax. Proguanil combined with atovaquone is sold under the tradename Malarone (GlaxoSmithKline).

Precautions[edit]

General precautions regarding proguanil involve watching out for feelings of sullenness and anxiety to a level outside the ordinary, when taking it over a period of several months.[citation needed] These may come on gradually and may not be immediately attributable to anything in particular.

Mechanism[edit]

One mode of action involves cyclization to form cycloguanil,[7] which binds to the dihydrofolate reductase of the parasite and inhibits the folic acid metabolism. However, proguanil itself may have an alternative mechanism of antimalarial action besides dihydrofolate reductase inhibition.[8]

See also[edit]

References[edit]

  1. ^ "Malarone (atovaquone/proguanil) Tablets, Pediatric Tablets. Full Prescribing Information" (PDF). GlaxoSmithKline. Research Triangle Park, NC 27709. Retrieved 14 July 2016. 
  2. ^ Carrington, HC; Crowther, AF; Davey, DG; Levi, AA; Rose, FL (22 December 1951). "A Metabolite of 'Paludrine' with High Antimalarial Activity". Nature. 168 (4286): 1080. doi:10.1038/1681080a0. PMID 14910643. 
  3. ^ Crowther, AF; Levi, AA (March 1953). "Proguanil—the Isolation of a Metabolite with High Antimalarial Activity". British Journal of Pharmacology and Chemotherapy. 8 (1): 93–7. doi:10.1111/j.1476-5381.1953.tb00758.x. PMC 1509229free to read. PMID 13066702. 
  4. ^ "WHO Model List of Essential Medicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  5. ^ Sutherland, CJ; Laundy, M; Price, N; Burke, M; Fivelman, QL; Pasvol, G; Klein, JL; Chiodini, PL (20 November 2008). "Mutations in the Plasmodium falciparum cytochrome b Gene are Associated with Delayed Parasite Recrudescence in Malaria Patients Treated with Atovaquone-Proguanil". Malaria Journal. 7 (1): 240. doi:10.1186/1475-2875-7-240. PMC 2640403free to read. PMID 19021900. Retrieved 14 July 2016. 
  6. ^ Payen, C; Monnin, L; Pulce, C; Descotes, J (March 2010). "Bone Marrow Aplasia Following Acute Poisoning with Chloroquine-Proguanil". Clinical Toxicology. 46 (10): 1085–7. doi:10.1080/15563650601182925. PMID 19065311. 
  7. ^ Arfeen, M; Patel, DS; Abbat, S; Taxak, N; Bharatam, PV (30 October 2014). "Importance of Cytochromes in Cyclization Reactions: Quantum Chemical Study on a Model Reaction of Proguanil to Cycloguanil". Journal of Computational Chemistry. 35 (28): 2047–55. doi:10.1002/jcc.23719. PMID 25196060. 
  8. ^ Thapar, MM; Gupta, S; Spindler, C; Wernsdorfer, WH; Björkman, A (May 2003). "Pharmacodynamic Interactions Among Atovaquone, Proguanil and Cycloguanil against Plasmodium falciparum in vitro". Transactions of the Royal Society of Tropical Medicine and Hygiene. 97 (3): 331–7. doi:10.1016/S0035-9203(03)90162-3. PMID 15228254.