Proguanil
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| Systematic (IUPAC) name | |
|---|---|
|
1-(4-chlorophenyl)-2-(N'-propan-2-ylcarbamimidoyl) guanidine | |
| Clinical data | |
| Trade names | Paludrine |
| AHFS/Drugs.com | Micromedex Detailed Consumer Information |
| Routes of administration | Oral |
| Pharmacokinetic data | |
| Metabolites | cycloguanine |
| Biological half-life | ~20 h |
| Identifiers | |
| CAS Number |
500-92-5  |
| ATC code | P01BB01 (WHO) |
| PubChem | CID 4923 |
| DrugBank |
DB01131 |
| ChemSpider |
4754 |
| UNII |
S61K3P7B2V |
| KEGG |
D08428 |
| ChEBI |
CHEBI:8455 |
| ChEMBL |
CHEMBL1377 |
| Chemical data | |
| Formula | C11H16ClN5 |
| Molar mass | 253.731 g/mol |
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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.
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.[3]
Medical uses
Proguanil is usually taken in combination with another antimalarial drug, such as atovaquone[4] (e.g. in the combination Malarone) or chloroquine.[5]
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
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. These may come on gradually and may not be immediately attributable to anything in particular.
Mechanism
One mode of action involves cyclization to form cycloguanil,[6] which binds to the DHFR enzyme of the parasite and inhibits the folic acid metabolism. However, proguanil itself may have an alternative mechanism of antimalarial action besides dihydrofolate reductase inhibition.[7]
See also
References
- ↑ Carrington HC, Crowther AF, Davey DG, Levi AA, Rose FL (1951). "A metabolite of paludrine with high antimalarial activity". Nature 168 (4288): 1080. doi:10.1038/1681080a0. PMID 14910643.
- ↑ Crowther AF, Levi AA (1953). "Proguanil, the isolation of a metabolite with high antimalarial activity". Br J Pharmacol Chemother 8 (1): 93–97. doi:10.1111/j.1476-5381.1953.tb00758.x. PMC 1509229. PMID 13066702.
- ↑ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
- ↑ 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.
- ↑ 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.
- ↑ Importance of cytochromes in cyclization reactions: Quantum chemical study on a model reaction of proguanil to cycloguanil. Minhajul Arfeen, Dhilon S Patel, Sheenu Abbat, Nikhil Taxak, Prasad V Bharatam, Journal of Computational Chemistry, 2014, 35, 28, 2047-2055
- ↑ Thapar, M. G.; Gupta, S.; Spindler, C.; Wernsdorfer, W. H.; 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): 331–337. doi:10.1016/S0035-9203(03)90162-3. ISSN 0035-9203. PMID 15228254.
External links
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