Pharmacological Studies on Clostridial Neurotoxins
Abstract
Studies have been done that involve synthetic as well as naturally occurring clostridial neurotoxin antagonists. Ammonium chloride (1-8 mM) and methylamine hydrochloride (1-16 mM) produced concentration-dependent antagonism of the onset of neuromuscular blockade caused by botulinum toxin types A, B and C and by tetanus toxin. Neither drug antagonized the onset of paralysis caused by Beta-bungarotoxin or by taipoxin. At concentrations that produced antagonism of clostridial neurotoxins, ammonium chloride and methylamine hydrochloride (8- 10 mM) did not inactivate toxin molecules, nor did they produce irreversible changes in tissue function. When studied under conditions that impose partial synchrony on the mechanism of clostridial neurotoxin action, ammonium chloride and methylamine hydrochloride did not inhibit ligand binding and did not reverse neuromuscular blockade. The drugs acted solely to antagonize internalization of toxins by cholinergic nerve endings. As a result of inhibiting the process of internalization, the drugs trapped the toxins at an antitoxin sensitive site. Tetanus toxin, fragment B and fragment C were assayed for toxicity on the mouse phrenic nerve-hemidiaphragm preparation. Homogenates of mouse cerebral cortex adsorbed tetanus toxin, and these homogenates competed with phrenic nerves for unbound toxin, but homogenized cortex did not displace or promote desorption of toxin already bound to phrenic nerves. Homogenates of eel and torpedo electric organ were not very effective in adsorbing toxin.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1983
- Accession Number
- ADA168488
Entities
People
- Lance L. Simpson
Organizations
- Columbia University