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Neuropharmacological Characterization of Botulinum Neurotoxin.
Final rept. 30 Mar 90-31 Dec 93,
JEFFERSON MEDICAL COLL PHILADELPHIA PA
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Studies have been done in three general areas i study of the mechanism of action of botulinum neurotoxin, ii identification of drugs that antagonize botulinum neurotoxin action, and iii extension of basic science studies on toxin action to the human nervous system. The two principal tissue preparations used were the mouse phrenic nerve-hemidiaphragm and the human pyramidalis muscle. The major findings were i stimulation of transglutaminase activity is not likely to be relevant to clostridial toxin action, ii zinc chelators, such as TPEN, are intracellular antagonists of all clostridial neurotoxins, iii inihibitors of vascuolar adenosine triphosphatase, such as bafilomycin, antagonize all clostridial neurotoxins but not phospholipase A2 neurotoxins, and iv human neuromuscular junctions are sensitive to all botulinum serotypes associated with natural poisoning e.g. , A, B, and E, and they are also sensitive to one serotype that is not typically associated with natural poisoning e.g., C.
APPROVED FOR PUBLIC RELEASE