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PubMed1995

Sterilisation of Babesia canis infections by imidocarb alone or in combination with diminazene.

Babesia canis infections were apparently sterilised by a single dose of imidocarb at 7.5 mg kg-1, as well as by a single dose of diminazene at 3.5 mg kg-1, followed by a single dose of imidocarb at 6 mg kg-1 the following day. This was confirmed by subinoculation of blood from these dogs to splenectomised recipients. Sterilisation of the infection is not recommended in endemic areas; a more rational approach would be to allow a state of premunity to develop in dogs at risk to repeated infections.

Animals↗
PubMedDate not supplied

Efficacy of Trypan: a diminazene based drug as antileishmanial agent.

Trypan, a diamidine based drug, was tested as an antileishmanial agent. Duplicate cultures of both Leishmania major and Leishmania donovani promastigotes in M199 medium and Trypan at various concentrations were tested. The cultures were incubated at 25 degrees C and parasites counted at 48 h interval, and the data generated was used to establish growth inhibition curves. Drug-free cultures were included to serve as control. In the in vivo study, a total of 40 BALB/c mice were divided into five groups of 8 mice each. They were infected with 2 x 10(6) promastogotes on the left footpad. Two groups were treated with 70 microg/ml of Trypan, a total of 500 microl used immediately after infection, one group by topical application and the other administered intraperitoneally. The treatments were repeated for the two other groups 10 weeks post infection, one by topical application and the other administered intraperitoneally. One group was not treated and thus served as control. Footpad sizes were measured using Vernier calliper every 2 weeks for 21 weeks. In the in vitro studies, Trypan inhibited growth of either L. major or L. donovani promastigotes in all the concentrations tested with more dramatic inhibition in high concentrations. Based on the in vivo studies, it was evident that Trypan had effect on L. major infected lesions when applied topically immediately after infection. However, there was no effect when treatment commenced after the lesions were established. The data is discussed.

Administration, Topical↗
PubMed2004

Degradation of berenil (diminazene aceturate) in acidic aqueous solution.

The trypanocide berenil was assessed for chemical stability over the pH range 1-8 at 37 degrees C and 0.2 M ionic strength. It was found to be sufficiently unstable under acid conditions that its therapeutic efficacy is most likely severely compromised when administered orally. At pH 3, the half-life was 35 min, decreasing to 1.5 min at pH 1.75. Reaction rate constants were corrected for the effects of buffer catalysis and were found to range from 2.00 min(-1) at pH 1 to 6.1 x 10(-6) min(-1) at pH 8. The pH-rate profile displayed a region (pH 1-4) where specific acid catalysis was dominant, followed by a transitional region (pH 5-7), and finally a region (pH >7) where uncatalysed degradation was most important. It is recommended that berenil be enteric coated for formulations to be used in treating Third World parasitic diseases.

Benzamidines↗
PubMed1993

An in vitro assay for drug sensitivity of Trypanosoma congolense using in vitro-derived metacyclic trypanosomes.

The sensitivity of seven populations of T. congolense to the salts of three trypanocides, diminazene, isometamidium and homidium, were determined in vitro using in vitro-derived metacyclic trypanosomes. The trypanosomes were incubated at 35 degrees C for 48 h with various drug concentrations (0.5 ng-50 micrograms/ml) and then transferred to cultures containing bovine endothelial-cell monolayers, to assess their viability over the following 5 days as compared to control trypanosomes that had been incubated without drug. The sensitivity to each drug was expressed as the minimum effective drug concentration which killed 100% of the trypanosomes in a given population within the 5 days. Using this assay, population IL 1180, characterised as being highly sensitive to all three drugs in vivo, required 10 ng/ml isometamidium chloride, 50 ng/ml homidium bromide or chloride and 5000 ng/ml diminazene aceturate to kill the entire population in vitro. In contrast, two derivatives of IL 1180 in which resistance to isometamidium had been induced in mice, IL 3343 and IL 3344, required isometamidium chloride at a concentration of 1000 ng/ml and 2000 ng/ml, respectively, to eliminate the populations. The in vitro results showed that the increase in level of resistance to isometamidium in these populations was associated with at least a 200-fold increase in resistance in both populations to homidium, but no increase in resistance to diminazene. KE 2887 and CP 81, two isolates expressing high levels of resistance to both isometamidium and homidium in mice and cattle, were both resistant in vitro to isometamidium chloride and homidium salts at 100 ng/ml. Furthermore, while the former population was resistant to 10,000 ng/ml diminazene aceturate, the latter was sensitive to 5000 ng/ml. IL 3274 and IL 3330, characterised as expressing high levels of resistance to all three drugs in vivo, were shown to be resistant to isometamidium chloride and homidium salts at 1000 ng/ml, and to diminazene aceturate at 10,000 ng/ml. Finally, the in vitro IC100 (concentration of drug required to eliminate 100% of the population) results were consistent with the maximum amounts of each drug detected in vivo.

Animals↗