Diminazene

Diminazene
Clinical data
Trade names	Azidin, Berenil, Ganasag, Pirocide
Other names	4,4'-(1-Triazene-1,3-diyl)bis(benzenecarboximidamide)
Routes of; administration	IM, SC
ATCvet code	QP51DF01 (WHO) ;
Legal status
Legal status	Veterinary use only;
Identifiers
	IUPAC name 4-[2-(4-Carbamimidoylphenyl)iminohydrazinyl]benzenecarboximidamide;
CAS Number	536-71-0; aceturate: 908-54-3;
PubChem CID	2354;
ChemSpider	2264;
UNII	Y5G36EEA5Z; aceturate: JI8SAD85NO;
ChEBI	CHEBI:81724 ;
ChEMBL	ChEMBL124025 ;
CompTox Dashboard (EPA)	DTXSID7043792 ;
ECHA InfoCard	100.007.860
Chemical and physical data
Formula	C14H15N7
Molar mass	281.323 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1=CC(=CC=C1C(=N)N)N/N=N/C2=CC=C(C=C2)C(=N)N;
	InChI InChI=1S/C14H15N7/c15-13(16)9-1-5-11(6-2-9)19-21-20-12-7-3-10(4-8-12)14(17)18/h1-8H,(H3,15,16)(H3,17,18)(H,19,20); Key:XNYZHCFCZNMTFY-UHFFFAOYSA-N;

Diminazene (INN; also known as diminazen) is an anti-infective medication for animals that is sold under a variety of brand names. It is effective against certain protozoa such as Babesia, Trypanosoma, and Cytauxzoon. The drug may also be effective against certain bacteria including Brucella and Streptococcus.^[1]^[2] Chemically it is a di-amidine and it is formulated as its aceturate salt, diminazene aceturate.

The mechanism is not well understood; it probably inhibits DNA replication,^[1] but also has affinity to RNA. The drug is known to change the structure of kinetoplast DNA in the Trypanosoma cruzi parasite, which causes Chagas' disease. In particular, kinetoplasts from parasites exposed to the drug have more densely linked minicircles, leading to the formation of fibers within the networks. ^[3]

Side effects

Acute side effects include vomiting, diarrhea, and hypotension (low blood pressure). Diminazen can harm the liver, kidneys and brain, which is potentially life-threatening; camels are especially susceptible to these effects.^[1]

Resistance

The Gibe River Valley in southwest Ethiopia showed universal resistance between July 1989 and February 1993.^[4] This likely indicates a permanent loss of function in this area against the tested target, T. congolense isolated from Boran cattle.^[4]

References

1 2 3 Peregrine AS, Mamman M (September 1993). "Pharmacology of diminazene: a review". Acta Tropica. 54 (3–4): 185–203. doi:10.1016/0001-706X(93)90092-P. PMID 7902657.
↑ Mungube EO, Vitouley HS, Allegye-Cudjoe E, Diall O, Boucoum Z, Diarra B, et al. (August 2012). "Detection of multiple drug-resistant Trypanosoma congolense populations in village cattle of south-east Mali". Parasites & Vectors. 5 155. doi:10.1186/1756-3305-5-155. PMC 3432589. PMID 22852796.
↑ Zuma AA, Cavalcanti DP, Zogovich M, Machado AC, Mendes IC, Thiry M, et al. (February 2015). "Unveiling the effects of berenil, a DNA-binding drug, on Trypanosoma cruzi: implications for kDNA ultrastructure and replication". Parasitology Research. 114 (2): 419–430. doi:10.1007/s00436-014-4199-8. hdl:2268/173546. PMID 25349143.
1 2 Mulugeta W, Wilkes J, Mulatu W, Majiwa PA, Masake R, Peregrine AS (April 1997). "Long-term occurrence of Trypanosoma congolense resistant to diminazene, isometamidium and homidium in cattle at Ghibe, Ethiopia". Acta Tropica. 64 (3–4). Elsevier BV: 205–217. doi:10.1016/s0001-706x(96)00645-6. PMID 9107367. S2CID 23878484.

[Peregrine-1] 1 2 3 Peregrine AS, Mamman M (September 1993). "Pharmacology of diminazene: a review". Acta Tropica. 54 (3–4): 185–203. doi:10.1016/0001-706X(93)90092-P. PMID 7902657.

[2] Mungube EO, Vitouley HS, Allegye-Cudjoe E, Diall O, Boucoum Z, Diarra B, et al. (August 2012). "Detection of multiple drug-resistant Trypanosoma congolense populations in village cattle of south-east Mali". Parasites & Vectors. 5 155. doi:10.1186/1756-3305-5-155. PMC 3432589. PMID 22852796.

[b270-3] Zuma AA, Cavalcanti DP, Zogovich M, Machado AC, Mendes IC, Thiry M, et al. (February 2015). "Unveiling the effects of berenil, a DNA-binding drug, on Trypanosoma cruzi: implications for kDNA ultrastructure and replication". Parasitology Research. 114 (2): 419–430. doi:10.1007/s00436-014-4199-8. hdl:2268/173546. PMID 25349143.

[Mulugeta-et-al-1997-4] 1 2 Mulugeta W, Wilkes J, Mulatu W, Majiwa PA, Masake R, Peregrine AS (April 1997). "Long-term occurrence of Trypanosoma congolense resistant to diminazene, isometamidium and homidium in cattle at Ghibe, Ethiopia". Acta Tropica. 64 (3–4). Elsevier BV: 205–217. doi:10.1016/s0001-706x(96)00645-6. PMID 9107367. S2CID 23878484.

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