Clinically available chemical antagonists of snake
neurotoxins still await to be identified. In this study, we demonstrate that an anti-
trypanosomiasis agent,
suramin, is an effective inhibitor of
beta-bungarotoxin isolated from the
venom of Formosan Krait snake. Following
intraperitoneal injection (12 ng/g) of
beta-bungarotoxin in mice, the time to
paralysis (loss a limb withdrawal reflex, 21. 8+/-3.4 h, n=4) was significantly prolonged after
intravenous injection (16 microg/g) of
suramin (35.9+/-4.0 h, n=4, P<0.05). The mechanism of this inhibitory effect of
suramin was analyzed at the mouse nerve terminals.
beta-Bungarotoxin (1 microg/ml) produces an irreversible blocking effect of nerve-evoked muscle contractions of mouse phrenic nerve-diaphragm (blocking time 135+/-6 min, n=6). Pretreatment with
suramin (0.3 mM) significantly prolonged the blocking time by three-fold. This selective inhibitory effect of
suramin was further confirmed when
suramin was shown to delay the neuromuscular blocking effect of another presynaptic
neurotoxin,
crotoxin (from American
rattlesnake venom), but not that of the postsynaptic
neurotoxin,
alpha-bungarotoxin. Furthermore,
suramin inhibited
beta-bungarotoxin in blocking transmitter release as revealed by prolonging the time to abolish the end-plate potential amplitude (with
suramin, 391+/-8 min; without treatment, 141+/-5 min). K(+) current was measured in the mouse triangularis sterni preparation;
suramin (0.3 mM) had no significant effect on
beta-bungarotoxin in inhibiting K(+) current (77+/-3% of control; with
suramin 75+/-3% of control, respectively). These findings clearly show that
suramin is an inhibitor of presynaptic
neurotoxins, mediated by interrupting the toxins in blocking the releasing mechanism of transmitter at the motor nerve terminals. The implication of these findings is that
suramin and related compounds can become useful agents in management of
snakebites.