Proguanil

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Proguanil
Proguanil Structural Formulae.png
Proguanil sf.png
Systematic (IUPAC) name
1-(4-chlorophenyl)-2-(N'-propan-2-ylcarbamimidoyl) guanidine
Clinical data
Trade names Paludrine
AHFS/Drugs.com Micromedex Detailed Consumer Information
Legal status ?
Routes Oral
Pharmacokinetic data
Half-life ~20 h
Identifiers
CAS number 500-92-5 YesY
ATC code P01BB01
PubChem CID 4923
DrugBank DB01131
ChemSpider 4754 YesY
UNII S61K3P7B2V YesY
KEGG D08428 YesY
ChEBI CHEBI:8455 YesY
ChEMBL CHEMBL1377 YesY
Chemical data
Formula C11H16ClN5 
Mol. mass 253.731 g/mol
 YesY (what is this?)  (verify)

Proguanil (chlorguanide, chloroguanide) is a prophylactic antimalarial drug.[1][2] When taken, it is converted to the active metabolite cycloguanil. 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.

Mechanism[edit]

It works by stopping the malaria parasites, Plasmodium falciparum and Plasmodium vivax, from reproducing once they are inside red blood cells, by inhibiting the enzyme dihydrofolate reductase, which catalyzes the formation of tetrahydrofolate, the main one-carbon unit carrier in the body, required for dTMP and purine base synthesis.

Combinations[edit]

Proguanil is usually taken in combination with another antimalarial drug, such as atovaquone[3] (e.g. in the combination Malarone) or chloroquine.[4]

Malarone 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.

References[edit]

  1. ^ Carrington HC, Crowther AF, Davey DG, Levi AA, Rose FL (1951). "A metabolite of paludrine with high antimalarial activity". Nature 168 (4288): 1080. PMID 14910643. 
  2. ^ Crowther AF, Levi AA (1953). "Proguanil, the isolation of a metabolite with high antimalarial activity". Br J Pharmacol Chemother 8 (1): 93–97. PMC 1509229. PMID 13066702. 
  3. ^ Sutherland CJ, Laundy M, Price N, et al. (November 2008). "Mutations in the Plasmodium falciparum cytochrome b gene are associated with delayed parasite recrudescence in malaria patients treated with atovaquone-proguanill". Malar. J. 7 (1): 240. doi:10.1186/1475-2875-7-240. PMC 2640403. PMID 19021900. 
  4. ^ Payen C, Monnin L, Pulce C, Descotes J (December 2008). "Bone marrow aplasia following acute poisoning with chloroquine-proguanil". Clin Toxicol (Phila) 46 (10): 1085–7. doi:10.1080/15563650601182925. PMID 19065311. 

External links[edit]