Benznidazole

Structural formula
General
Non-proprietary name	Benznidazole
other names	N -Benzyl-2-nitroimidazol-1-ylacetamide
Molecular formula	C 12 H 12 N 4 O 3
External identifiers / databases
EC number	624-902-4
ECHA InfoCard	100.153.448
PubChem	31593
ChemSpider	29299
DrugBank	DB11989
Wikidata	Q425300
Drug information
ATC code	P01 CA02
Drug class	Antiprotozoic
properties
Molar mass	260.25 g · mol -1
Physical state	firmly
Melting point	189 ° C
solubility	400 mg l −1 in water
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 315-319-335
	P: 261-305 + 351 + 338
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Benznidazole (trade name including Rochagan ( BR ); first manufacturer Hoffmann-La Roche ) is a drug from the nitroimidazole group that is used in the treatment of the acute phase of Chagas disease .

Clinical information

Benznidazole is recommended by the WHO for the treatment of acute Chagas disease. The effectiveness in chronic illnesses is controversial and is currently being tested in a clinical study co-financed by the WHO. The use of benznidazole is limited by sometimes considerable side effects. Thrombocytopenic purpura and agranulocytosis are most serious ; in such cases, therapy must be stopped immediately.

Pharmacological properties

Benznidazole works by generating free radicals during its metabolism. The causative agent of Chagas disease, Trypanosoma cruzi , is very sensitive to free radicals because enzymes for breaking down such radicals are lacking or have only low activity. In animal studies, damage to the adrenal gland, large intestine and esophagus was observed after administration of benznidazole. Benznidazole is considered to be mutagenic and carcinogenicity has been shown in some non-clinical studies, but there was no evidence of such effects in humans in treated patients. The nitro group of the substance must be enzymatically reduced for the toxic effect.

Other Information

Benznidazole was developed by Roche in the early 1970s (Ro-71051). Along with nifurtimox, it has been the standard therapy for Chagas disease in Latin America since the early 1980s ; the WHO has added benznidazole to the list of indispensable drugs . Benznidazole preparations are not approved in Europe; In the USA, benznidazole is approved in the form of 12.5 mg and 100 mg tablets; in Latin America, benznidazole is commercially available in the form of tablets of 100 mg.

In 2003 Roche donated the patent and remaining drugs to Lafepe , a Brazilian state-owned company .

At the beginning of December 2015 it was announced that hedge fund manager Martin Shkreli and his company KaloBios Pharmaceuticals Inc had obtained the rights to benznidazole in the USA from Savant Neglected Diseases LLC . Appropriate approval in the USA is to be achieved within a year.

Individual evidence

↑ ^a ^b Entry on benznidazole in the ChemIDplus database of the United States National Library of Medicine (NLM) .
↑ ^a ^b sheet benznidazole at Sigma-Aldrich , accessed on 10 March 2011 ( PDF ).
↑ WHO Chagas disease , accessed on 13 August 2012 found.
↑ Study on benznidazole in chronic Chagas disease .
↑ ^a ^b Castro et al .: "Toxic side effects of drugs used to treat Chagas' disease (American trypanosomiasis)", Hum Exp Toxicol . 2006 Aug , 25 (8) , pp. 471-479, PMID 16937919 .
^ ^A ^b Rodriques Coura J., de Castro SL: "A critical review on Chagas disease chemotherapy. Mem Inst Oswaldo Cruz." 2002 Jan , 97 (1) , pp. 3-24. PMID 11992141 .
↑ Maya et al .: Mode of action of natural and synthetic drugs against Trypanosoma cruzi and their interaction with the mammalian host . In: Comp Biochem Physiol A Mol Integr Physiol . 2007 Apr , 46 (4) , pp. 601-620, PMID 16626984 .
↑ NDA: 209570
^ ^A ^b Andrew Pollack: "Martin Shkreli's Latest Plan to Sharply Raise Drug Price Prompts Outcry" of December 11, 2015.
↑ Amrutha Penumudi: "Shkreli's KaloBios buys Chagas disease drug rights, shares soar" Reuters of December 3, 2015.

[ChemID-1] Entry on benznidazole in the ChemIDplus database of the United States National Library of Medicine (NLM) .

[Sigma-2] sheet benznidazole at Sigma-Aldrich , accessed on 10 March 2011 ( PDF ).

[3] WHO Chagas disease , accessed on 13 August 2012 found.

[4] Study on benznidazole in chronic Chagas disease .

[Castro-5] Castro et al .: "Toxic side effects of drugs used to treat Chagas' disease (American trypanosomiasis)", Hum Exp Toxicol . 2006 Aug , 25 (8) , pp. 471-479, PMID 16937919 .

[Coura-6] A ^b Rodriques Coura J., de Castro SL: "A critical review on Chagas disease chemotherapy. Mem Inst Oswaldo Cruz." 2002 Jan , 97 (1) , pp. 3-24. PMID 11992141 .

[7] Maya et al .: Mode of action of natural and synthetic drugs against Trypanosoma cruzi and their interaction with the mammalian host . In: Comp Biochem Physiol A Mol Integr Physiol . 2007 Apr , 46 (4) , pp. 601-620, PMID 16626984 .

[8] NDA: 209570

[nyt111215-9] A ^b Andrew Pollack: "Martin Shkreli's Latest Plan to Sharply Raise Drug Price Prompts Outcry" of December 11, 2015.

[10] Amrutha Penumudi: "Shkreli's KaloBios buys Chagas disease drug rights, shares soar" Reuters of December 3, 2015.