Disease relevance of Isometamidium chloride

• Ethidium and isometamidium induce the breakdown of intracellular adenosine triphosphate in Ehrlich ascites tumor cells incubated in vitro [1].
• In mice the 50% curative doses (CD50) for Samorin range from 0.007 to 20 mg/kg body weight [2].
• Field evaluation of the prophylactic effect of an isometamidium sustained-release device against trypanosomiasis in cattle [3].
• The control of bovine trypanosomiasis in Africa continues to rely heavily on the chemoprophylactic drug isometamidium (ISMM) chloride [4].
• An intramuscular dose (1.0 mg/kg) of Samorin 3 weeks post-infection significantly reduced the parasitemia in adult chinook [5].

High impact information on Isometamidium chloride

• Pentamidine, diminazene aceturate (Berenil), isometamidium chloride (Samorin), and ethidium bromide, which are important antitrypanosomal drugs, promote linearization of Trypanosoma equiperdum minicircle DNA (the principal component of kinetoplast DNA, the mitochondrial DNA in these parasites) [6].
• The accumulation and compartmentalization of isometamidium chloride in Trypanosoma congolense, monitored by its intrinsic fluorescence [7].
• The results therefore indicate that the alteration of fluorescence is due to interaction of isometamidium with an intracellular component(s) and that isometamidium is transported across the plasma membrane via a protein carrier [8].
• Antrycide and isometamidium were both non-competitive inhibitors of diamine oxidase, having Ki values of 6 X 10(-9) M and 3 X 10(-9) M respectively [9].
• Point mutations in mitochondrial topoisomerase enzymes of Trypanosoma congolense are not involved in isometamidium resistance [10].

Chemical compound and disease context of Isometamidium chloride

• As few as two isometamidium treatments one month apart were associated with significant weight loss, and cattle treated with diminazene aceturate after three or four isometamidium treatments suffered a 50% mortality [11].
• Influence of atropine on the acute toxicity of isometamidium [12].
• The protection of 80 Nigerian trade cattle from trypanosomiasis and liver flukes using Samorin 1 and Trodax 2 [13].

Biological context of Isometamidium chloride

• A mathematical model has been developed which was able to predict theoretical lines representing the uptake kinetics in trypanosomes which were sensitive to isometamidium, as well as for resistant trypanosomes in which reduced accumulation was a result of either reduced uptake or enhanced efflux of the drug [14].
• The overall absolute bioavailability of intramuscular-administered isometamidium was 65.7% [15].
• Pharmacokinetics of the chemoprophylactic and chemotherapeutic trypanocidal drug isometamidium chloride (Samorin) in cattle [15].
• The presence of the insertion, specifying an extra codon was found to always be present in the genomes of T. congolense clones that were resistant to isometamidium chloride [16].
• Only 6 (2.8%) of 212 serum samples from trypanosome-infected cattle had serum levels of the drug above 0.4 ng isometamidium per ml serum which is indicative for drug resistance in the infecting parasite population [17].

Anatomical context of Isometamidium chloride

• Some effects of the trypanocidal drug isometamidium on encapsulation in bovine carrier erythrocytes [18].
• This suggests that some C. salmositica switched from aerobic respiration to glycolysis when the mitochondrion was damaged by isometamidium [19].
• A preliminary study on the absorption of isometamidium chloride (Samorin) in the stomach and small intestine of rat [20].
• Metabolism of isometamidium in hepatocytes isolated from control and inducer-treated rats [21].
• Binding of isometamidium to calf thymus DNA and lipids: pharmacological implications [22].

Associations of Isometamidium chloride with other chemical compounds

• Susceptibility of a rodent-adapted strain of Trypanosoma vivax to Berenil, Samorin and Novidium [23].
• In spite of the need for more frequent treatment in the homidium group as compared to the isometamidium group, total drug costs were lower in the former [24].
• In contrast, the isometamidium-resistant T. b. brucei stocks showed the mutant-type sequence patterns with six point mutations that had previously been reported in a laboratory-derived arsenical-resistant T. brucei strain [25].
• In vivo and in vitro sensitivity of Trypanosoma evansi and T. equiperdum to diminazene, suramin, MelCy, quinapyramine and isometamidium [26].
• Thirty-six Trypanosoma brucei spp. stocks isolated from man and domestic animals in south-east Uganda were studied for susceptibility to diminazene, isometamidium and melarsoprol in vitro [27].

Gene context of Isometamidium chloride

• A drug-resistant Trypanosoma congolense strain with predetermined curative doses (CD50 and CD90) of samorin at 13.9 +/- 1.02 and 20.3 +/- 1.13 mg/kg body weight, respectively, was cyclically transmitted through tsetse flies and by syringe passages in mice in the absence of drug pressure [28].
• An isolate from a buffalo in Ha bac province (Hb1) was the least sensitive with trypamidium at a CD80 > 128 mg/kg, more than 8 times the CD 100 of the remaining isolates (16 mg/kg) [29].
• Analyses were made on the adenosine transporter-1 gene in Trypanosoma brucei (TbAT1), encoding a P2-like nucleoside transporter, from T. brucei brucei field stocks to investigate a possible link between the presence of mutations in this gene and isometamidium resistance [25].
• To analyse the restriction fragment length polymorphism pattern of a fragment of TbAT1 (nucleotides 430-1108), the 677-bp polymerase chain reaction products from eight of the isometamidium-sensitive and two of the isometamidium-resistant T. b. brucei were subjected to digestion with Sfa NI [25].
• In cattle treated with both trypanocides, weight loss and serum glutamate dehydrogenase levels were correlated with isometamidium concentrations [11].

Analytical, diagnostic and therapeutic context of Isometamidium chloride

• Evaluation and improvement of an enzyme-linked immunosorbent assay for the detection of isometamidium in bovine serum [4].
• These findings were consistent with extensive tissue binding at the intramuscular injection site to form a primary depot responsible for most of the prolonged chemoprophylactic effect of isometamidium, and an additional role for significant secondary drug depots formed by tissue binding elsewhere, particularly after intravenous administration [15].
• A simple competitive enzyme immunoassay for the detection of the trypanocidal drug isometamidium [30].
• Although there was no clear indication of underestimation of the weight of the animals and although farmers had adequate knowledge of the correct usage of isometamidium, the results suggest frequent underdosing when considering isometamidium serum concentrations 1 week after treatment [31].
• Solid-phase extraction and ion-pair reversed-phase HPLC of isometamidium in bovine serum and tissues [32].

References