Methyglyoxal bis (guanylhydrazone) (
MGBG) at 0.5 mM had little effect in vitro on Blastocrithidia culicis, Crithidia oncopelti, and Leishmania spp., but completely inhibited growth of Trypanosoma brucei. Inhibition became irreversible after a 3-h exposure of T. brucei culture procyclics. Treated organisms remained motile, but failed to divide.
Polyamines,
spermidine, and
spermine, did not reverse the anti-trypanosome action of
MGBG (preloading of cells or concurrent administration). Two
intraperitoneal injections of the
drug at a concentration of 50 mg/kg
body weight at a 1-day interval greatly reduced the
parasitemia of T. brucei and T. congolense in rats. Trypanosome
infections, however, relapsed and killed the animals in 6 days
after treatment. It was evident from the results of tracer experiments with T brucei that MGBF significantly lowered incorporation of [3H]
thymidine by culture pocyclics and of [3H]
uridine by bloodstream forms; in both stages [3H]
leucine incorporation was only slightly inhibited. It is suggested that
MGBG interferes with
nucleoside incorporation by Trypanosoma and that its mode of action is different in bloodstream and culture procyclics.