Sodium stibogluconate is a medicine used to treat leishmaniasis and is only available for administration by injection. It belongs to the class of medicines known as the pentavalent antimonials. Sodium stibogluconate is sold in the UK as Pentostam (manufactured by GlaxoSmithKline). Widespread resistance has limited the utility of sodium stibogluconate, and in many parts of the world, amphotericin or miltefosine are used instead. It is also being investigated as an anti-tumor agent.
For the treatment of various types of a protozoal infection called leishmaniasis, which may result from sandfly bites in tropical and temperate parts of the world. Also investigated for use/treatment in cancer/tumors (unspecified) and solid tumors.
The mode of action of sodium stibogluconate is not clearly understood. In vitro exposure of amastigotes to 500 mg pentavalent antimony/ml results in a greater than 50% decrease in parasite DNA, RNA protein and purine nucleoside triphosphate levels. It has been postulated that the reduction in ATP (adenosine triphosphate) and GTP (guanosine triphosphate) synthesis contributes to decreased macromolecular synthesis.
Mechanism of action
Sodium stibogluconate directly inhibits DNA topoisomerase I leading to inhibition of both DNA replication and transcription.
Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphot...
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Chakraborty AK, Majumder HK: Mode of action of pentavalent antimonials: specific inhibition of type I DNA topoisomerase of Leishmania donovani. Biochem Biophys Res Commun. 1988 Apr 29;152(2):605-11. [PubMed:2835038 ]
Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]
Drug created on November 18, 2007 11:26 / Updated on June 11, 2017 16:42