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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-12-17
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
382
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
75-80
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Suramin inhibits the toxic effects of presynaptic neurotoxins at the mouse motor nerve terminals.
pubmed:affiliation
Institute of Pharmacology, College of Medicine, National Taiwan University, No. 1, Sec 1, Jen-Ai Road, Taipei, Taiwan.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't